Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.52227202
BP ALL reacted highly specifically with P190bcr abl but not with P210bcr abl isolated from chronic myeloid leukemia cell lines . 0.52227202^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.91861052
We have examined the ability of additional SH 2 domains to bind phosphotyrosine free BCR and compared this with their ability to bind tyrosine phosphorylated c ABL 1b . 0.91861052^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.94406307
Biological activities of BCR ABL , an activated tyrosine kinase oncogene responsible for pathogenesis of human leukemias , can be completely inactivated by a deletion of the BCR aminoterminal sequence with tetramerizing property ( BCR ABL delta 1 40 ) . 0.94406307^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.5915413
We show that c Abl associates with and phosphorylates the BCR coreceptor CD 19 , and that c Abl and CD 19 colocalize in lipid membrane rafts . 0.5915413^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.66568038
Overexpression of Bcr has been shown to inhibit the Bcr Abl oncoprotein , and the endogenous Bcr protein forms a complex with c Abl in hematopoietic cells and insect cells . 0.66568038^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.66792792
The archetypical disease in this regard is chronic myeloid leukemia , where abl is constitutively activated by fusion with the bcr gene ( bcr / abl ) . 0.66792792^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We therefore sought evidence for analogous point mutations in the ABL gene in patients with Ph negative , BCR negative CML ( n = 25 ) , Ph negative ALL ( n = 18 ) and in Ph positive CML in transformation ( n = 28 ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
These data provide evidence for rapid divergent clonal evolution and selection of B cell progenitors initiated by BCR / ABL p 190 , followed by other , secondary genetic events mirroring similar changes in the equivalent , highly malignant human leukemia Philadelphia ( Ph ) positive / B precursor acute lymphoblastic leukemia ( ALL ) . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In addition we show the reactivity of BP 2 with bcr abl proteins in leukemic cells of a Philadelphia chromosome positive ALL patient . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The investigations of BCR / ABL rearrangement on molecular level are an important tool for differential diagnosis of lymphoblastic crisis of CML and ALL and also are very valuable in detection of residual Ph positive cells in cytogenetic conversion of CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Approximately five percent of pediatric acute lymphoblastic leukemias ( ALL ) contain a translocation ( 9 ; 22 ) ( q 34 ; q 11 ) which results in rearrangement of the bcr and abl genes . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Detection of BCR / ABL translocation by polymerase chain reaction in leukemic progenitor cells ( ALL CFU ) from patients with acute lymphoblastic leukemia ( ALL ) . ^^^ In about 30 % of cases , BCR / ABL transcripts are present in freshly isolated mononuclear cells from the bone marrow of patients with acute lymphoblastic leukemia ( ALL ) using the polymerase chain reaction ( PCR ) technique . ^^^ In all of them , BCR / ABL transcripts were detected at initial diagnosis . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We conclude that Ph negative BCR / ABL positive ALL is very rare entity if existing at all . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The polymerase chain reaction ( PCR ) has become a standard method for highly sensitive detection of the bcr / abl rearrangement in patients with chronic myelogenous leukemia ( CML ) or acute lymphoblastic leukemia ( ALL ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We examined the expression of P 190 type bcr / abl in single hematopoietic colonies obtained at various clinical stages of a patient with Ph 1 positive ALL , using the polymerase chain reaction ( PCR ) . ^^^ These results suggest transformation of multipotential stem cell in this patient and confirm that expression of the P 190 type bcr / abl fusion gene permits stem cell differentiation leading to Ph 1 positive ALL . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
It is reasonable to suggest that this might be the case by analogy with other known pathologies , such as class 1 oncogenes activated by transduction by retroviruses , abnormal expression of EGF receptors or deregulated activity of c abl encoded proteins in CML and ALL . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The development of PCR based methods for the detection of the bcr / abl mRNA associated with the Philadelphia chromosome has improved our understanding of the significance and incidence of this disease marker in ALL , emphasizing the importance of establishing Philadelphia status on all patients at diagnosis . ^^^ Although longitudinal studies in CML have shown the presence of bcr / abl mRNA to be associated with residual disease , and its absence associated with long term remission , these studies have yet to be reported for ALL . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Evidence for a potential selective effect of SF culture was obtained by a leukaemic progenitor cell assay ( ALL CFU ) and the detection of the bcr / abl translocation by polymerase chain reaction ( PCR ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
It is well established that fusion of bcr and abl genes plays a crucial role in the pathogenesis of CML and ALL . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In this review , molecular genetic constructions of ABL , BCR and BCR ABL hybrid genes in CML , as well as m BCR ABL hybrid gene in Ph 1 positive ALL are focused in detail . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Probes for a potential selective effect were brought through leukemic progenitor cell assay ( CFU ALL ) and the polymerase chain reaction ( PCR ) study of the bcr / abl translocation . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Transposition of the abl gene was demonstrated in seven Philadelphia ( Ph ' ) negative patients with either chronic myeloid leukaemia ( CML ) or acute lymphocytic leukaemia ( ALL ) by chromosomal in situ hybridization . ^^^ In six out of seven CML patients and one out of two ALL patients , a significant accumulation of abl hybridization grains was localized to chromosome 22 . ^^^ Transposition of abl was not apparent in one patient with Ph ' negative CML and in one patient with Ph ' negative ALL . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The results confirm the presence of the ABL protein P 210 in all cases of CML , ALL and AML positive for rearrangement in the bcr region of chromosome 22 , and , surprisingly , in one AML case apparently negative for bcr rearrangement . ^^^ The ABL protein P 190 was found to be present only in cases of ALL negative for bcr rearrangement . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Daley et al ( 1990 ) induced CML in mice by bone marrow transplantation of cells infected with a retrovirus encoding P210bcr / abl and Heisterkamp et al ( 1990 ) produced mice transgenic for a BCR / ABL P 190 DNA construct and showed that the progeny died of acute leukaemia ( mostly ALL ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In lymphoblastic leukemias , there are two molecular subtypes of the Ph 1 chromosome , one with a rearrangement of the breakpoint cluster region ( bcr ) of the BCR gene , producing the same 8 . 5 kilobase BCR ABL fusion mRNA seen in chronic myelogenous leukemia ( CML ) , and the other , without a bcr rearrangement , producing a 7 . 0 kilobase BCR ABL fusion mRNA that is seen only in acute lymphoblastic leukemia ( ALL ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Identification of the Ph 1 acute lymphoblastic leukemia ( ALL ) has become possible by studying abl oncogene in Ph 1 positive ALL . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Although the c abl is translocated and a new 190 kd c abl protein has been identified , no breakpoints are observed in the bcr ( Ph+bcr ALL ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Our data indicate that in ALL abl is translocated into the 5 ' region of the bcr gene . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Studies from this laboratory and others have shown that virtually all patients with chronic myelogenous leukemia have this new bcr / abl fusion gene . ^^^ In contrast to these findings in chronic myelogenous leukemia , a small number of patients with Ph 1 ( + ) acute lymphoblastic leukemia ( ALL ) have been studied and were found to lack the bcr / abl fusion gene [ bcr ( ) ] , but to have a new activation of abl , by recombination with an as yet undetermined region on chromosome 22 . ^^^ In this study , nine adults with Ph 1 ( + ) ALL have been examined for evidence of a bcr / abl fusion gene . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We have determined the prevalence of amplification and rearrangements for c myc , c myb , c mos , bcr , c abl , c Ha ras 1 , c N ras , and c K ras 2 in a total of 51 cases of human leukaemia ( 19 patients with AML , 13 cases with CML , 14 cases with ALL , and 5 cases with CLL ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
All cases examined showed the same joining of the first exon of the bcr gene to the c abl oncogene . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In most cases of CML and some cases of Ph+ ALL the protooncogene ABL from 9q34 is translocated to the breakpoint cluster region ( bcr ) of the BCR gene at 22q11 to form a chimeric gene encoding a novel 210 kd protein ( P 210 BCR ABL ) with enhanced tyrosine kinase activity . ^^^ In other patients with Ph+ ALL and Ph+ AML , the breakpoint probably occurs in the first intron of the BCR gene ; this results in a smaller chimeric gene which encodes a P 190 BCR ABL . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
To understand the nature of the breakpoints on chromosome 22 in bcr rearrangement negative , Ph ' positive ALLs , we have cloned and sequenced the cDNA of the c abl oncogene in such ALL cells . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Particularly in pediatric Ph positive ALL , the majority of cases show a c abl oncogene translocation without bcr rearrangement . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Recently , the absence of bcr rearrangement and expression of a distinct aberrant 190 kd abl protein ( p190c abl ) has been described in Ph positive ALL , with the suggestion that the two abl variants may be pathogenetically associated with myeloid 5 lymphoid leukemogenesis . ^^^ Here we report that the genomic configuration and translation product of Ph positive AML can be similar to that of Ph positive ALL : the break at 22q11 may occur outside the 5 . 8 kb bcr region and result in expression of a 190 kD abl protein lacking these bcr sequences . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
However , in spite of all these research efforts , the precise role of the ABL gene in normal and neoplastic growth remains to be determined . ^^^ The elucidation of ABL function by a variety of approaches such as those described above will ultimately aid in the development of far reaching therapeutic treatments for at least two forms of human leukaemia : Ph positive CML and Ph positive ALL . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In some cases of Ph 1 positive ALL , a novel abl related protein ( P190all abl ) of 190K has been shown to have tyrosine kinase activity . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We studied molecular events related to bcr and c abl in five patients with ALL to determine its relationship to CML . ^^^ These data suggest that Ph 1 chromosome positive ALL is heterogeneous ; in some patients the molecular abnormality is identical to CML ; in others c abl is likewise involved but via a different mechanism . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
A combination of monosomy 7 and translocation t ( 9 ; 22 ) ( q 34 ; q 11 ) , rarely observed in acute lymphoblastic leukaemia ( ALL ) , is here reported : a peculiarity of this case was that the `` breakpoint cluster region ' ' on chromosome 22 was not rearranged , as demonstrated by molecular analysis , and a new c abl protein ( p 190 ) was found , instead of the usual p 210 protein usually associated with the Ph chromosome ; moreover a rearrangement of c abl oncogene was found . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In addition , we observed normal size bcr and c abl transcripts in an ALL cell line carrying the t ( 9 ; 22 ) translocation . ^^^ We conclude , therefore , that if c abl is inappropriately expressed in ALL cells without bcr rearrangements , the genetic mechanism of activation must be different from that reported for CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Among the `` src family , ' ' c fes was expressed more in AML than ALL , and c abl was expressed at variable but not elevated levels in all leukemia types . c Ha ras was uniformly expressed at low levels , as in non neoplastic cells . c Ki ras transcription was detected only in T ALL ; N ras expression was barely demonstrable . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Expression of a distinctive BCR ABL oncogene in Ph 1 positive acute lymphocytic leukemia ( ALL ) . ^^^ The Ph 1 chromosome in ALL expresses a distinct ABL derived 7 kilobase messenger RNA that encodes the P185ALL ABL protein . ^^^ Since the expression of different oncogene products may play a role in the distinctive presentation of Ph 1 positive ALL versus CML , it is necessary to understand the molecular basis for the expression of P185ALL ABL . ^^^ Nucleotide sequence analysis of complementary DNA clones made from RNA from the Ph 1 positive ALL SUP B 15 cell line , and S 1 nuclease protection analysis confirmed the presence of BCR ABL chimeric transcripts in Ph 1 positive ALL cells . ^^^ In Ph 1 positive ALL , ABL sequences were joined to BCR sequences approximately 1 . 5 kilobases 5 ' of the CML junction . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Using in situ hybridization , we demonstrate that in accordance with observations in CML the Ph 1 chromosome in ALL patients is the result of a consistent translocation of the c abl oncogene to the Ph 1 chromosome . ^^^ Northern blot analysis using RNA from three Ph 1 positive ALL patients revealed that in the leukemic cells of two patients larger c abl mRNA transcripts were present , as in CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Translocations affecting the structure of the c abl proto oncogene are involved in the development or progression of chronic myelogenous leukemia ( CML ) and acute lymphocytic leukemia ( ALL ) . ^^^ Analysis of the functions of these new molecules may provide insight into mechanisms by which oncogenic abl proteins participate in the etiology of CML and ALL . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We have recently identified a common ALL patient which harboured a chromosomal fusion between the TEL gene on chromosome 12 and the ABL gene on chromosome 9 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Here we report a patient with chromosomally normal bone marrow , in all 60 cells analysed , who was found to have the p 210 type BCR ABL chimaeric transcript by RT / PCR . ^^^ We conclude that molecular and cytogenetic methods should be used in conjunction to detect the BCR ABL gene rearrangement in ALL . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Of adverse influence are delayed time to reach CR ( more than 4 / 5 weeks ) , a high initial white blood cell count , higher age ( above 50 or 60 years ) , and probably the immunological subtypes pre T ALL , pre B ALL , My ( + ) ALL ; of very adverse influence in elderly patients is the karyotype t ( 9 ; 22 ) or the corresponding BCR / ABL gene rearrangement . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Two ALL patients without ( ALL / My ) and three with myeloid antigens ( ALL / My+ ) also demonstrated bcr / abl rearrangement . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Unique forms of the abl tyrosine kinase distinguish Ph 1 positive CML from Ph 1 positive ALL . ^^^ We report that Ph 1 positive ALL cells express unique abl derived tyrosine kinases of 185 and 180 kilodaltons that are distinct from the bcr abl derived P 210 protein of CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Our proposal is that most , and probably all , variants of Ph 1 are complex translocations involving part of 9q34 and that the conjunction of a specific region of 22q11 with a specific segment of 9q34 ( carrying the c abl protooncogene ) is essential for the development of Ph 1 + CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BCR / ABL chimeric transcript , which was positive in BM samples before purging , was shown to be absent after ex vivo purging in all three cases tested . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We designed a new semi quantitative competitor based PCR assay to assess the amount of p 190 BCR ABL mRNA in patients with Ph positive ALL . ^^^ We measured the number of ABL transcripts / micrograms RNA in all samples as an internal standard in order to control for variations in sample quality and other parameters . ^^^ We conclude that in general , blood and marrow contain similar BCR ABL transcript numbers in Ph positive ALL but some samples are discordant . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We report a girl with Ph 1 positive ALL with the aberrant BCR ABL product . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
A Ph+ acute myeloid leukaemia expressing both CML type and ALL type BCR / ABL mRNA transcripts . ^^^ Reverse transcriptase polymerase chain reaction ( RT PCR ) analysis revealed the presence of two BCR / Abl mRNA transcripts ; b2a2 , the CML type and E1a2 , the ALL type . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
A 41 year old female patient with a pre B ALL expressing 2 BCR / ABL transcripts e1 / a2 and b2 / a2 underwent autologous bone marrow transplantation ( aBMT ) with marrow grown in long term culture ( LTC ) for consolidation of remission ( CR ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Recognition of the ALL specific BCR ABL junction in P190bcr abl by monoclonal antibody ER FP 1 . ^^^ Ph chromosome positive ALL is correlated with a bad prognosis , therefore the detection of chimeric BCR ABL proteins is of prime importance in ALL diagnosis . ^^^ Immunological double staining experiments using ER FP 1 and a monoclonal antibody recognizing all BCR ABL proteins confirmed the specificity of ER FP 1 for the e 1 a2 fusion point . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
All these patients received intensive conventional chemotherapy and during early recovery from marrow aplasia , when the WBC reached 0 . 5 2 . 0 10 10 ( 9 ) / L , BPC were collected by 4 8 leukapheresis and tested for the persistence of the marker translocations and , when possible , for the presence of the hybrid bcr / abl transcripts by polymerase chain reaction ( PCR ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The cytosolic 185 and 210 kDa Bcr Abl protein tyrosine kinases play important roles in the development of Philadelphia chromosome positive ( Ph+ ) chronic myelogenous leukemia ( CML ) and acute lymphoblastic leukemia ( Ph+ ALL ) . p 185 and p 210 Bcr Abl contain identical abl encoded sequences juxtaposed to a variable number of bcr derived amino acids . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
These results suggest that a specific inhibitor of bcr / abl kinase could be an effective antileukemic agent against Ph 1 positive CML or ALL . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The presence of BCR ABL fusion genes has important diagnostic and prognostic implications in chronic myeloid leukemia ( CML ) and acute lymphoblastic leukemia ( ALL ) . ^^^ BCR ABL fusion was detected in all cases with high specificity ( false positive nuclei : mean , 0 . 1 % ) . ^^^ In conclusion , hybridization with D107F9 and cos abl 8 allows unambiguous diagnosis of BCR ABL genes and is likely to become an important tool for the monitoring of therapies in patients with CML and ALL . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Establishment and characterization of a new Ph 1 positive ALL cell line ( ALL / MIK ) presenting bcr gene rearrangement on bcr 2 and ALL type bcr / abl transcript : suggestion of in vitro differentiation to monocytoid lineage . ^^^ Consistent with this result , the reverse transcriptase dependent polymerase chain reaction ( RT PCR ) assay revealed that the ALL / MIK cells contained the transcript derived fusion of the first exon of bcr gene and the second exon of abl gene . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Identification of masked and variant Ph ( complex type ) translocations in CML and classic Ph in AML and ALL by fluorescence in situ hybridization with the use of bcr / abl cosmid probes . ^^^ In the present study , three chronic myelogenous leukemia ( CML ) patients with variant Philadelphia ( Ph ) chromosomes ( complex types ) , two CML patients with a masked Ph , one case with Ph positive acute lymphocytic leukemia ( ALL ) , and one with Ph positive acute myelocytic leukemia ( AML ) were analyzed by standard cytogenetic techniques ( G banding ) , Southern blot studies , and fluorescence in situ hybridization ( FISH ) procedures using probes from portions of the bcr and abl genes . ^^^ Our results demonstrate that this FISH assay can also detect the bcr / abl fusion status in CML patients with masked or variant ( complex type ) Ph chromosomes and in some patients with Ph positive ALL or AML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Several important issues in CML research are not covered in this brief review such as the structural or molecular basis of the translocation between ABL and BCR , the relationship between CML and ALL with an identical or related BCR / ABL abnormality , the biology of CML stem and progenitor cells and immunologic aspects of CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Molecular quantitative Polymerase Chain Reaction ( PCR ) techniques have been developed to detect low levels of leukemic cells in patients with diseases characterised by fusion transcripts . 95 % of Chronic Myelocytic ( CML ) and 15 25 % of Acute Lymphoblastic Leukemia ( ALL ) patients are Ph 1 producing a fusion transcript between the abl proto oncogene and the bcr gene . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The application of fluorescent in situ hybridization to detect Mbcr / abl fusion in variant Ph chromosomes in CML and ALL . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We report a case of pre B cell acute lymphoblastic leukemia ( ALL ) with the Ph 1 chromosome , t ( 9 ; 22 ) translocation and P 190 associated BCR / ABL rearrangement . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Using this new assay we have identified a patient with benign phase CML who produces P 190 BCR ABL , the form of the BCR ABL protein found in about 50 % of cases of acute lymphocytic leukemia ( ALL ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Maximal specificity is presumably achieved when the DNA sequences amplified are truly leukaemia specific , such as BCR / ABL in chronic myelogenous leukemia , RARA PML / RARA in t ( 15 ; 17 ) acute myelogenous leukemia , DEK / CAN in t ( 6 ; 9 ) AML , PBX1 / E2A in t ( 1 ; 19 ) acute lymphoblastic leukemia ( ALL ) , or TAL 1 deletions in other T ALLs . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We found a 5 . 4 % incidence of BCR / ABL rearrangement positive cases in pre B and c ALL in childhood . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Both retained the Ph 1 chromosome and expressed the ALL type bcr / abl chimeric mRNA containing the junction of the first exon of BCR gene ( e 1 ) and second exon of c abl gene ( a 2 ) . ^^^ Taken together , the 2 cell lines had features of Ph 1 positive ALL : ( 1 ) hematopoietic progenitor cells with pre B cell phenotype and , ( 2 ) activation of e 1 a2 type bcr / abl oncogene without alterations of p 53 gene . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Finally , the relationship between the two common forms of BCR / ABL , the P 190 and P 210 configurations , and different disease phenotypes , like CML and Philadelphia ( Ph 1 ) chromosome positive acute lymphoblastic leukemia ( ALL ) , needs to be clarified . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The E2A / PBX1 and the BCR / ABL fusion genes result from the t ( 1 ; 19 ) ( q 23 ; p 13 ) and the t ( 9 ; 22 ) ( q 34 ; q 11 ) , respectively , and encode oncoproteins which are thought to play an important role in the development of acute lymphoblastic leukemia ( ALL ) subtypes associated with adverse prognosis . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We have now used the same technique , reverse transcription / polymerase chain reaction amplification of ABL BCR transcripts , to study nine patients with Philadelphia ( Ph ) chromosome positive acute lymphoblastic leukemia ( ALL ) ; seven expressed the P 190 and two the P 210 type of BCR ABL fusion protein . ^^^ All seven patients with P 190 had ABL BCR transcripts containing a junction between ABL exon Ib and BCR exon 2 ( Ib e 2 ) ; in two cases , ABL BCR transcripts with the Ia e 2 junction type were also present . ^^^ Of the two P 210 ALL patients , one had a Ib b 4 ABL BCR transcript and the other showed no detectable ABL BCR expression . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
All patients tested for the bcr / abl rearrangement by reverse transcriptase polymerase chain reaction ( RT PCR ) were negative 4 weeks post BMT . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
This genomic structure is of interest because of its analogy to the organization of the ABL gene and because this part of the gene is not affected by the breakpoints occurring in Ph 1 positive acute lymphoblastic leukemia ( ALL ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic myelogenous leukemia ( CML ) and some acute lymphoblastic leukemias ( ALL ) are caused by the t ( 9 ; 22 ) chromosome translocation , which produces the constitutively activated BCR / ABL tyrosine kinase . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Incidence and clinical outcome of children with BCR / ABL positive acute lymphoblastic leukemia ( ALL ) . ^^^ Immunophenotypic studies at diagnosis in 21 BCR / ABL positive children identified common ALL in 16 patients ( 76 . 2 % ) , pre B ALL in four ( 19 . 0 % ) , and an early T lineage ALL in one ( 4 . 8 % ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Southern blot analysis revealed no rearrangement in Mbcr 1 , and direct sequencing of the PCR product confirmed it to be the ALL type mbcr 1 fusion mRNA with the first exon of the BCR gene fused to ABL exon a 2 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Fusion of the N terminal 426 amino acids of Bcr generates p 190 ( Bcr Abl ) which is mostly found in acute lymphocytic leukemia ( ALL ) , whereas fusion of the N terminal 902 or 927 amino acids of Bcr generates p 210 ( Bcr Abl ) mostly found with chronic myelogenous leukemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Of 144 adult Eastern Cooperative Oncology Group ( ECOG ) patients with acute lymphoblastic leukemia ( ALL ) entered on study E 2993 at the time of analysis , 104 had informative immunophenotypes and molecular analysis by polymerase chain reaction for BCR / ABL fusion transcripts . ^^^ In 23 patients ( 22 % ) , BCR / ABL transcripts were detected : the ALL typical e1a2 alone in 12 , e1a2 + b2a2 / b3a2 in five , and b2a2 and / or b3a2 in six . ^^^ Of BCR / ABL positive patients , 83 % had early pre B ALL , one patient had pre T ALL , while half of the BCR / ABL negative patients had early pre B ALL , 18 % had CD 10 negative pro B ALL and 21 % were pre T . ^^^ Therefore , CD 25 expression may serve as a surrogate marker for BCR / ABL positivity ( Philadelphia chromosome ) , the major poor prognostic parameter in adult ALL . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The smallest of the fusion proteins , p190BCR ABL , ( m bcr breakpoint ) is principally associated with Ph positive ALL . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Growth inhibition was also observed with a p185BCR ABL positive acute lymphocytic leukemia ( ALL ) cell line generated from a Philadelphia chromosome positive ALL patient . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We analyzed 40 samples of peripheral blood and bone marrow ( CML , 16 ; acute myelogenous leukemia , 6 ; acute lymphoblastic leukemia [ ALL ] , 1 ; chronic lymphoblastic leukemia , 2 ; myelodysplasias , 4 ; myeloproliferative disorders , unclassified , 3 ; nonleukemic hematologic malignancies , 3 ; hypercellular bone marrow , 1 ; normal control samples , 2 ; and K 562 cell line samples , 2 ) for the presence of bcr abl fusion gene and its messenger RNA ( mRNA ) transcript by FISH and RT PCR , respectively . ^^^ Thirty three samples were evaluable by FISH ; 14 of 14 evaluable CML samples and one ALL sample were positive for bcr abl by FISH ( 100 % ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Both chronic myelogenous leukemias ( CML ) and a subset of acute lymphoblastic leukemias ( ALL ) are associated with the expression of BCR / ABL proteins . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The Philadelphia chromosome ( Ph ) translocation generates a chimeric tyrosine kinase oncogene , BCR / ABL , which causes chronic myelogenous leukemia ( CML ) and a type of acute lymphoblastic leukemia ( ALL ) . ^^^ In primary samples from virtually all patients with CML or Ph+ALL , the CRKL adapter protein is tyrosine phosphorylated and physically associated with p 210 ( BCR / ABL ) . ^^^ Here we demonstrate that another cellular protein linked to BCR / ABL through the CRKL SH 2 domain is p 130 ( CAS ) . p 130 ( CAS ) was found to be tyrosine phosphorylated and associated with CRKL in BCR / ABL expressing cell lines and in samples obtained from CML and ALL patients , but not in samples from controls . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Bcr Abl is an oncogenic tyrosine kinase expressed in tumor cells of CML and a subset of ALL which in its unregulated and activated state is thought to cause cell transformation and leukemia . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
This la Ph , expressing an acute lymphoblastic leukemia ( ALL ) type BCR / ABL transcript , produces a novel P180BCR / ABL fusion protein reflecting deletion of 174 bases ( 58 amino acids ) encoded by the a 2 exon of the ABL gene . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Patients with CML in blast crisis , or with Philadelphia positive acute lymphoblastic leukaemia ( ALL ) , can have a smaller BCR ABL fusion transcript possessing only the first exon of BCR fused to ABL . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
P210BCR ABL protein was detected by Western blotting in platelet lysates of 12 / 13 CML patients with active disease but not in the lysate of platelets from a Ph positive acute lymphoblastic leukaemia ( ALL ) patient in remission or eight BCR ABL negative controls including one essential thrombocythaemia ( ET ) patient . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Molecular analysis has documented BCR ABL fusion genes in three apparently Ph chromosome negative cell lines , all three derived from CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Twenty four adult Chinese patients with de novo acute lymphoblastic leukemia ( ALL ) were studied for the BCR / ABL translocation using both conventional cytogenetics and fluorescence in situ hybridization ( FISH ) . ^^^ To conclude , the frequency of BCR / ABL translocation in Chinese patients with de novo ALL is comparable to patients in the Western hemisphere , in contrast to a previous report . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
RT PCR analysis of diagnostic marrow revealed the presence of three bcr / abl transcripts ; the ALL type ela 2 along with the CML types , b2a2 and b3a2 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We have described an unusual case of ALL in which ETV 6 is found fused to the ABL gene ; ABL is normally activated by fusion to the BCR gene in the 9 : 22 translocation . ^^^ We expanded the primary cells from this ETV6 / ABL rearranged case of ALL in SCID animals and analyzed them for expression of both ETV6 / ABL and the normal ETV 6 mRNA . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The value of dual color fluorescence in situ hybridization ( FISH ) with BCR and ABL probes for the detection of the Philadelphia ( Ph ) translocation and of other alterations involving ABL and / or BCR was evaluated in adult acute lymphoblastic leukemia ( ALL ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
PATIENTS AND METHODS : The BCR / ABL gene ( p 210 and p 190 ) was prospectively studied by nested RT PCR in 17 adult patients diagnosed with ALL BCR / ABL positive cases were monitored by RT PCR and cytogenetic techniques over the treatment period ( LAL 93 AR protocol ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
ALL and CML type BCR / ABL mRNA transcripts in chronic myelogenous leukemia and related disorders . ^^^ Using the reverse transcription polymerase chain reaction , we investigated acute lymphoid leukemia ( ALL ) type , and chronic myelogenous leukemia ( CML ) type BCR / ABL mRNA expression in a total of 66 patients with chronic myeloproliferative disorder ( CMPD ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We analysed 20 patients with BCR ABL positive acute lymphoblastic leukaemia ( ALL ) by quantitative competitive polymerase chain reaction ( QC PCR ) to study the kinetics of the leukaemic clone . ^^^ In all samples , total ABL transcripts were measured as internal control , and the percentage of BCR ABL / ABL molecules was calculated . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Retrospective molecular analyses of the pre treatment pre B cell ALL sample showed the b3a2 ( p 210 ) and e1a2 ( p 190 ) BCR / ABL fusion transcripts . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Our present study demonstrated that PRAME was markedly expressed in primary leukemic cells with chronic myeloid leukemia ( CML ) in blastic crisis and Philadelphia ( Ph ) + acute lymphoblastic leukemia ( ALL ) , in which BCR / ABL played an important role as a pathogenic gene . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Cytokine supplemented suspension cultures of leukemic blasts in 98 patients with AML and five patients with ALL ( normal karyotype , n = 2 ; BCR / ABL , n = 3 ) were performed . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Along a 5 year period in a single institution , specific molecular markers were prospectively looked for in consecutive patients with acute leukemia , by means of polymerase chain reaction ( PCR ) : In patients with acute lymphoblastic leukemia ( ALL ) , the BCR / ABL and TEL AML 1 fusion transcripts as well as clonotypic immunoglobulin gene rearrangements were investigated , whereas in patients with acute myelogenous leukemia ( AML ) the PML RAR alpha , AML 1 ETO and CBF beta MYH 11 fusion proteins were assessed . ^^^ Specific molecular markers were identified in 15 / 75 patients : Four with ALL ( three with clonotypic IgG rearrangements and one with BCR / ABL ) and 11 with AML ( nine with the PML / RAR alpha fusion protein M 3 AML , and two with the AML1 / ETO fusion protein M 2 AML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Double fusion signal BCR / ABL , detected by FISH on chromosomes 9 and 22 in a child with ALL . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BACKGROUND : The BCR / ABL and MLL / AF4 fusion genes resulting from t ( 9 ; 22 ) ( q 34 ; q 11 ) and t ( 4 ; 11 ) ( q 21 ; q 23 ) translocations , respectively are considered as a high risk prognostic factors in children with acute lymphoblastic leukaemia ( ALL ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In nearly all French American British leukemia subtypes , we found p 15 methylation in bone marrow or peripheral blood cells from 58 % ( 46 / 79 ) of patients with acute myeloid leukemia ( AML ) , acute lymphoblastic leukemia ( ALL ) , or acute biphenotypic leukemia ( ABL ) . ^^^ According to cytogenetic data from 35 patients with ALL , AML , or ABL , 82 % ( 14 / 17 ) of those with unmethylated p 15 alleles had normal karyotypes or hyperdiploidies associated with a favorable prognosis . ^^^ Thirty nine of 43 blood samples ( 91 % ) sequentially collected from 12 patients with AML , ALL , or ABL showed p 15 methylation status in excellent concordance with morphologic disease stage . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In a patient with Philadelphia chromosome positive acute lymphoblastic leukaemia ( ALL ) , a novel variant of the chimaeric BCR ABL mRNA transcript was detected by reverse transcription polymerase chain reaction ( RT PCR ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The Bcr / Abl P 190 oncoprotein is responsible for the development of Philadelphia chromosome positive acute lymphoblastic leukemia ( ALL ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
ABL 1 methylation in Ph positive ALL is exclusively associated with the P 210 form of BCR ABL . ^^^ This raises the question of whether methylation of the ABL 1 promoter is an epigenetic modification also associated with Ph positive ALL . ^^^ To study this issue , we used methylation specific PCR and bisulfite sequencing to determine the methylation status of the ABL 1 promoter in 18 Ph positive ALL samples . ^^^ While six out of the seven P 210 positive ALL samples had ABL 1 promoter methylation , none of the 11 P 190 positive ALL samples demonstrated ABL 1 promoter methylation . ^^^ In addition , we estimated the extent and relative abundance of ABL 1 promoter methylation in several Ph positive ALL samples and compared it to the methylation pattern in chronic , accelerated and blastic crisis phases of CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
By employing a new semi quantitative assay system that includes co culturing leukemia cells with the mouse bone marrow derived stromal cell line MS 5 , we examined the suppressive effect of a selective inhibitor of ABL tyrosine kinase , STI 571 , on acute lymphoblastic leukemia ( ALL ) cells with BCR ABL fusion . ^^^ Leukemic blast cells from eight patients with B precursor ALL , including three patients with BCR ABL positive ALL , were cultured on monolayers of MS 5 cells for 3 weeks with or without addition of variable amounts of STI 571 . ^^^ In BCR ABL positive ALL patients , CA containing cells were examined by FISH , and all contained BCR ABL fusion genes . ^^^ STI 571 inhibited CA formation of BCR ABL positive ALL cells virtually 100 % at 0 . 1 1 . 0 micromol / l . ^^^ None of the five BCR ABL negative ALL patients showed this growth inhibition by STI 571 at 0 . 1 1 . 0 micromol / l . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BACH 2 was consistently upregulated ( 2 10 fold ) in all 10 Ph+ lymphoid lines tested following BCR / ABL inhibition . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chromosomal translocation t ( 9 ; 22 ) ( q 34 ; q 11 ) , found in 95 % of patients with chronic myeloid leukemia ( CML ) and 30 % of adult patients with acute lymphoblastic leukemia ( ALL ) generates a chimeric gene , BCR / ABL . ^^^ There are three kinds BCR / ABL fusion transcripts of p210BCR ABL found in CML and ALL , p190BCR ABL mainly in ALL , and p230BCR ABL in CML , either of which depends on the location of the breakpoints within the BCR gene . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic myeloid leukemia ( CML ) is a generic term that includes five subtypes ; i . e . chronic granulocytic leukemia ( CGL ) ( 95 % of all CML , 90 % are Ph+ , 5 % are Ph , BCR / ABL+ ) , atypical CML ( survival is worse than that of CGL ) , chronic myelomonocytic leukemia ( a subtype of myelodysplastic syndrome ) , chronic neutrophilic leukemia ( Ph , BCR / ABL ) and juvenile CML ( Ph , BCR / ABL ) . ^^^ In addition , about a half of cases with Ph positive ALL have the same size of BCR / ABL fusion protein as that in Ph positive CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
A case of Philadelphia ( Ph ) positive acute lymphoblastic leukemia ( ALL ) with multiple subclones including duplication of the BCR ABL 1 fusion gene and of the Abelson oncogene ( ABL 1 ) is reported . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Recent phase 1 and phase 2 studies in patients with bcr / abl positive CML and ALL showed a low rate of grade III / IV toxicity and good clinical efficacy . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BCR / ABL fluorescent in situ hybridization study of chronic myeloid leukemia ( CML ) and Philadelphia ( + ) ( Ph ( + ) ) acute lymphoid leukemia ( ALL ) indicated that approximately 9 % of patients exhibited an atypical hybridization pattern consistent with a submicroscopic deletion of the 5 ' region of ABL and the 3 ' region of the BCR genes on the 9q ( + ) chromosome . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Adult precursor B ALL with BCR / ABL gene rearrangements displays a unique immunophenotype based on the pattern of CD 10 , CD 34 , CD 13 and CD 38 expresssion . ^^^ At present , detection of BCR / ABL gene rearrangements is mandatory in precursor B ALL patients at diagnosis for prognostic stratification and treatment decision . ^^^ The aim of the present study was to explore the immunophenotypic characteristics of precursor B ALL cases displaying BCR / ABL gene rearrangements using multiple stainings analyzed by quantitative flow cytometry in order to rapidly ( < 1 h ) identify unique phenotypes associated with this translocation . ^^^ From the 82 precursor B ALL cases included in the study 12 displayed BCR / ABL gene rearragements , all corresponding to adult patients , four of which also displayed DNA aneuploidy . ^^^ Therefore , the combined use of staining patterns for CD 34 , CD 38 and CD 13 expression within CD 10 positive blast cells is highly suggestive of BCR / ABL gene rearrangements in adults with precursor B ALL . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BCR / ABL fusion tyrosine kinase is responsible for the initiation and maintenance of the Philadelphia chromosome ( Ph ( 1 ) ) positive chronic myelogenous leukemia ( CML ) and a cohort of acute lymphocytic leukemias ( ALL ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The Abl kinase inhibitor imatinib mesylate ( STI 571 ) has significant and rapid antileukemic activity in Philadelphia chromosome / Bcr Abl positive acute lymphoblastic leukemia ( Ph ( + ) ALL ) but such activity is usually of short duration except for a small proportion of patients . ^^^ To determine the prognostic significance of early Bcr Abl levels and changes in peripheral blood ( PB ) and bone marrow ( BM ) , serial samples of 56 patients with relapsed or refractory Ph ( + ) ALL treated in phase 2 trials of imatinib were analyzed by quantitative polymerase chain reaction ( PCR ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
To identify mechanisms of resistance to STI 571 , 30 complementary DNAs ( including 9 matched samples ) obtained from the bone marrow of individuals with Ph ( + ) ALL were analyzed by direct sequencing of a 714 base pair region of ABL encoding for the adenosine triphosphate ( ATP ) binding site and the kinase activation loop . ^^^ In conclusion , Ph ( + ) ALL samples resistant to STI 571 have a unique mutation Glu255Lys of BCR ABL . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
CONCLUSION : Interphase D FISH emerges as a reliable , fast and relatively inexpensive tool for the detection of BCR / ABL rearrangements in adult ALL patients at diagnosis . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
All 4 mutants , Delta ( 1 63 ) bcr / abl , ( 1 63 ) bcr / abl , Tyr177Phe bcr / abl , and ( 1 210 ) bcr / abl exhibited elevated tyrosine kinase activity and conferred factor independent growth in cell lines . ^^^ In contrast , differences in the transforming potential of the 4 mutants occurred in our mouse model , in which all mice receiving P 210 bcr / abl expressing bone marrow cells exclusively develop a myeloproliferative disease ( MPD ) resembling human CML . ^^^ The other 3 mutants , ( 1 63 ) bcr / abl , Tyr177Phe bcr / abl , and Delta ( 1 63 ) bcr / abl , failed to induce an MPD but instead caused T cell ALL . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We describe immunophenotype of : B lineage ALL with MLL rearrangements , TEL / AML1 , BCR / ABL , E2A / PBX1 translocations , hyperdiploidy , and myc fusion genes ; T ALL with SCL gene aberrations and t ( 5 ; 14 ) translocation ; and AML with AML1 / ETO , PML / RARalpha , OTT / MAL and CBFbeta / MYH11 translocations , trisomies 8 or 11 and aberrations of chromosomes 7 and 5 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Point mutations were found in the adenosine triphosphate ( ATP ) binding region of BCR / ABL in 12 of 18 patients with chronic myeloid leukemia ( CML ) or Ph positive acute lymphoblastic leukemia ( Ph ( + ) ALL ) and imatinib resistance ( defined as loss of established hematologic response ) , but they were found in only 1 of 10 patients with CML with imatinib refractoriness ( failure to achieve cytogenetic response ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We have prospectively monitored , by reverse transcription polymerase chain reaction ( RT PCR ) during follow up , the presence of the BCR / ABL fusion transcript in Ph+ ALL children diagnosed in the Italian multicentre Associazione Italiana Ematologia Oncologia Pediatrica ALL AIEOP 95 therapy protocol . ^^^ Within the PPR group , the RT PCR monitoring constantly showed positivity for the BCR / ABL fusion transcript and all the patients died of disease progression . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
OBJECTIVE : To study the expression of bcr / abl hybridized gene in chronic myeloid leukemia ( CML ) , acute lymphatic leukemia ( ALL ) and polycythemia vera ( PV ) , and its clinical significance . ^^^ Six ( 25 % ) of 24 ALL patients were positive for Bcr / abl fusion gene , which was negative in 2 PV patients . ^^^ Two ( 67 % ) of the 3 bcr / abl negative CML patients and 5 ( 87 % ) of the 6 bcr / abl positive ALL patients had refractory leukemia . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Imatinib mesylate , a signal transduction inhibitor that inhibits tyrosine kinase activity , the protein product of the ABL proto oncogene , has remarkable activity in patients with chronic myeloid leukemia ( CML ) and Philadelphia chromosome positive ( Ph ( + ) ) acute lymphoblastic leukemia ( ALL ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In Philadelphia chromosome positive ( Ph ( + ) ) acute lymphoblastic leukemia ( ALL ) , the BCR ABL translocation is the main transforming event , making it another hematologic malignancy targeted by this ABL tyrosine kinase inhibitor . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
DESIGN AND METHODS : In this study we adapted the multiplex RT PCR assay , previously described by Pallisgaard et al . , to detect all the most frequent genetic lesions with their characteristic splicing variants occurring in acute lymphoblastic leukemia , such as the MLL / AF4 , MLL / ENL , BCR / ABL p 190 ( e1a2 ) and p 210 ( b2a2 , b3a2 ) isoforms , E2A / PBX1 , TEL / AML1 , SIL / TAL1 and the novel NUP98 / RAP1GDS1 transcript , recently described in a T ALL leukemic subtype . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
A cohort of 72 patients with CML in myeloid blast crisis ( BC ) ( n = 34 ) , lymphoid BC ( n = 2 ) , accelerated phase ( AP ) ( n = 16 ) , CP ( n = 18 ) , and BCR ABL ( + ) acute lymphoblastic leukemia ( ALL ) ( n = 2 ) resistant to imatinib were investigated . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Clinico biologic features and treatment outcome of adult pro B ALL patients enrolled in the GIMEMA 0496 study : absence of the ALL1 / AF4 and of the BCR / ABL fusion genes correlates with a significantly better clinical outcome . ^^^ Our data demonstrate that in adult pro B ALL a distinction should be made between pro B ALL cases with and without the ALL1 / AF4 or the BCR / ABL chimeric genes , since the absence of both of these fusion genes correlates with a significantly better clinical outcome after intensive polychemotherapy treatment without hematopoietic stem cell transplantation . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Bcr Abl constitutes a deregulated tyrosine kinase involved in the pathogenesis of chronic myeloid leukemia ( CML ) and a subset of acute lymphoblastic leukemia ( ALL ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
This observation has important implications for the study of BCR / ABL ALL . ^^^ Notably , we found that the erythropoietin receptor ( EPOR ) is consistently highly expressed in TEL / AML1 ALL compared with BCR / ABL or MLL . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
OBJECTIVES : To investigate patients with acute lymphoblastic leukemia ( ALL ) for TEL / AML1 fusion , BCR / ABL fusion , MLL gene rearrangements , and numerical changes of chromosomes 4 , 10 , 17 and 21 by fluorescence in situ hybridization ( FISH ) and to determine the relationship and the significance of those findings . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Interphase fluorescence in situ hybridization ( iFISH ) is increasingly used for the identification of BCR / ABL gene rearrangements in chronic myeloid leukemia ( CML ) and acute lymphoblastic leukemia ( ALL ) . ^^^ In the present study , we have explored the incidence of both typical and atypical iFISH patterns of BCR / ABL gene rearrangements in a series of 168 consecutive BCR / ABL+ patients 135 CML , 31 precursor B ALL and two acute myeloblastic leukemia ( AML ) cases and established their underlying genetic alterations through further molecular and chromosome analyses . ^^^ Our results show that most BCR / ABL+ patients ( 83 % , including 88 % of all CML , 61 % of ALL and one of two AML ) displayed typical iFISH patterns of either Major ( M ) BCR / ABL ( 87 % of CML , 13 % of ALL and one of the two AML ) or minor ( m ) BCR / ABL gene rearrangements ( 1 % of all CML and 48 % of ALL cases ) with the two probes . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Surprisingly , almost all leukemic blasts at presentation turned out to possess the minor type of BCR / ABL fusion gene . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Ph ( + ) ALL cells harbor a bcrabl fusion gene ( e1a2 ) encoding a 190 kDa fusion protein ( p 190 ) involved in disease pathogenesis . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The ABL gene on chromosome band 9q34 is a proto oncogene and is the well known translocation partner of the BCR gene on 22q11 giving rise to t ( 9 ; 22 ) ( q 34 ; q 11 ) , which is the hallmark of chronic myeloid leukemia and is the most common chromosomal abnormality in adult acute lymphoblastic leukemia ( ALL ) . ^^^ The authors herein describe an 8 year old male patient with precursor T cell ALL harboring both ABL gene amplification and p 16 ( INK4a ) gene deletion . ^^^ This is the first report of an ALL case with ABL amplification , and the authors speculate that both ABL proto oncogene amplification and the p 16 ( INK4a ) tumor suppressor gene deletion have been implicated in leukemogenesis in the present case , although whether the ABL amplification truly contributes to the leukemogenesis or merely an epiphenomenon representing underlying genomic instability remains to be determined . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Imatinib , the ABL kinase inhibitor , is used not only for Philadelphia chromosome positive ( Ph + ) chronic myelogenous leukemia , but also for Ph + acute lymphoblastic leukemia ( ALL ) , although resistance to the drug tends to develop in an early stage of the clinical course . ^^^ We describe a childhood refractory Ph + ALL patient in whom progressive resistance to imatinib was correlated with the appearance of a mutation in the BCR ABL kinase domain and in vitro drug resistance to imatinib as determined by the methyl thiazol tetrazolium ( MTT ) assay . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The aims of this study were to estimate the incidences of BCR / ABL , MLL , TEL / AML1 rearrangements , and p 16 deletions in childhood acute lymphoblastic leukemia ( ALL ) , to identify new abnormalities , and to demonstrate the usefulness of interphase fluorescence in situ hybridization ( FISH ) . ^^^ We performed G banding analysis and FISH using probes for BCR / ABL , MLL , TEL / AML1 rearrangements , and p 16 deletions on 65 childhood ALL patients diagnosed and uniformly treated at a single hospital . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
However , resistance occurs especially in advanced phase CML and Ph+ ALL , primarily as a consequence of point mutations within the Bcr Abl kinase domain that prevent imatinib from binding . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We prospectively evaluated minimal residual disease ( MRD ) by measuring BCR / ABL levels with a quantitative real time PCR procedure after induction and after consolidation in 45 adults with Ph+ ALL who obtained complete hematological remission after a high dose daunorubicin induction schedule . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Fluorescence in situ hybridization for the BCR / ABL rearrangement in 138 bone marrow specimens from 59 Philadelphia ( + ) ( Ph ( + ) ) chronic myelogenous leukemia ( CML ) patients , 35 Ph ( + ) acute lymphoblastic leukemia ( ALL ) patients , and 57 Ph ( ) ALL patients was used . ^^^ ABL deletions were not detected among the 35 ALL patients ( 17 with major BCR / ABL , 18 with minor BCR / ABL ) , and it appears that this deletion occurs rarely or not at all in Ph ( + ) ALL patients , which is in contrast to the CML patients ( 27 . 1 % ) . ^^^ However , we detected two ALL cases with ABL deletion but without BCR / ABL rearrangement among 49 Ph ( ) ALL and 66 Ph ( ) AML patients . ^^^ ABL deletions were not detected among the 35 ALL patients ( 17 with major BCR / ABL , 18 with minor BCR / ABL ) , and it appears that this deletion occurs rarely or not at all in Ph ( + ) ALL patients , which is in contrast to the CML patients ( 27 . 1 % ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Granulocytic marker CD66c Carcinoembryonic antigen related cell adhesion molecule 6 ( CEACAM 6 ) is aberrantly expressed on ALL with strong correlation to genotype ( negative in TEL / AML1 and MLL / AF4 , positive in BCR / ABL and hyperdiploid cases ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The fusions , TEL / AML1 and BCR / ABL , and rearrangements of the MLL gene occurred at frequencies of 22 % ( n = 447 / 2027 ) ( 25 % in B lineage ALL ) , 2 % ( n = 43 / 2027 ) and 2 % ( n = 47 / 2016 ) respectively . ^^^ Amplification involving the ABL gene , a rare recurrent abnormality confined to T ALL patients , was identified for the first time . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Because of the importance in detecting t ( 9 ; 22 ) in ALL patients and because occasionally a cytogenetically cryptic BCR / ABL fusion is detected with fluorescence in situ hybridization ( FISH ) , our laboratory routinely performs BCR / ABL FISH tests on all newly diagnosed ALL patients . ^^^ A split ABL FISH signal without the involvement of BCR does not represent a t ( 9 ; 22 ) translocation , and prognostic implications of this apparent subgroup of ALL cases have not been determined . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Detectable by fluorescence in situ hybridization ( FISH ) , these losses of sequence include deletion of the 5 ' region of the ABL gene and the 3 ' region of BCR in chronic myeloid leukemia ( CML ) and acute lymphoblastic leukemia ( ALL ) , as well as the 5 ' region of ETO in acute myeloid leukemia ( AML ) French American British type M 2 associated with t ( 8 ; 21 ) , 3 ' MLL in AML and ALL , and 3 ' core binding factor beta ( CBFbeta ) in AML associated with inv ( 16 ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
ABL 1 amplification , due to a cryptic episomal translocation NUP214 / ABL1 , is a novel finding in T cell acute lymphoblastic leukemia ( ALL ) . ^^^ We reached the following conclusions : ( 1 ) FISH is the only technique that promptly identifies T cell ALL patients with ABL 1 amplification , ( 2 ) quick identification with FISH is fundamental in the clinic because this T cell ALL subset is imatinib sensitive but may become resistant due to development of additional mutations , and ( 3 ) ABL 1 quantitative RT PCR may be easily applied to monitor minimal residual disease . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In view of this unique mode of action , we examined the effects of adaphostin on numerous imatinib resistant leukemia models , including imatinib resistant CML and Ph+ ALL cell lines , cells harboring point mutations in BCR / ABL , and specimens from imatinib resistant CML patients , using assays for intracellular ROS , apoptosis , and clonogenicity . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We here show that BCR / ABL , but not FMS like tyrosine kinase 3 ( FLT 3 ) internal tandem duplication ( ITD ) transformed 32D cells or primary acute myeloid leukemia ( AML ) blasts undergo apoptosis after treatment with the HDI valproic acid ( VPA ) plus all trans retinoic acid ( VPA / ATRA ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
One hundred , thirty one ( 95 AML , 25 ALL , 11 ABL ) patients were studied . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The t ( 9 ; 22 ) ( q 34 ; q 11 ) translocation occurs in chronic myeloid leukemia ( CML ) and adult B cell acute lymphoblastic leukemia ( ALL ) , leading to fusion of BCR to ABL 1 and constitutive activation of ABL 1 tyrosine kinase activity . ^^^ P 190 BCR ABL 1 is found in the remaining two thirds of t ( 9 ; 22 ) positive adult B ALL cases but only exceptionally in CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Philadelphia ( Ph ) chromosome ( BCR / ABL ) positive ALL is particularly common among older patients . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic myelogenous leukaemia ( CML ) and Philadelphia chromosome positive ( Ph+ ) acute lymphoblastic leukaemia ( ALL ) are caused by the BCR ABL oncogene . ^^^ However , accelerated or blast crisis phase CML patients and Ph+ ALL patients often relapse due to drug resistance resulting from the emergence of imatinib resistant point mutations within the BCR ABL tyrosine kinase domain . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
A minor breakpoint region ( m bcr ) BCR / ABL rearrangement , corresponding to the fusion product gene p 190 , was detected by interphase FISH in 3 of these cases , Immunophenotyping analysis classified five of the 6 cases as B lineage ALL . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
This chromosome occurs as a consequence of a reciprocal translocation between the long arms of chromosomes 9 and 22 which results in the creation of a new gene comprising sequences from the c abl gene on chromosome 9 and the bcr gene on chromosome 22 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The polymerase chain reaction ( PCR ) can not be used to amplify the breakpoint in the chimaeric BCR ABL gene in CML and acute leukaemias due to the large variation in the sites of breakpoint in the BCR gene ( within a 5 . 8 kb region ) and in the ABL gene ( within a 150 kb region ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The hallmark of chronic myelogenous leukemia is the translocation of the human c abl protooncogene ( ABL ) from chromosome 9 to the specific breakpoint cluster region ( bcr ) of the BCR gene on chromosome 22 . ^^^ The t ( 9 ; 22 ) ( q 34 ; q 11 ) translocation results in the formation of a BCR ABL fusion gene that encodes a 210 kDa chimeric protein with abnormal tyrosine kinase activity . ^^^ The ABL and BCR genes are expressed by normal cells and thus the encoded proteins are presumably nonimmunogenic . ^^^ However , the joining region segment of the p210BCR ABL chimeric protein is composed of unique sequences of ABL amino acids joined to BCR amino acids that are expressed only by malignant cells . ^^^ The current study demonstrates that the joining region of BCR ABL protein is immunogenic to murine T cells . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Detection of bcr / c abl mRNA in chronic myelogenous leukemia by polymerase chain reaction to identify chromosome translocation . ^^^ The hallmark of chronic myelogenous leukemia ( CML ) is the Philadelphia chromosome ( Ph 1 ) which is caused by a translocation of the c abl gene from chromosome 9 to the breakpoint cluster region ( bcr ) on chromosome 22 . ^^^ Polymerase chain reaction ( PCR ) can be used to detect the chimeric bcr / c abl mRNA as evidence of the translocation . ^^^ We applied a very simple and quick method of isolating cytoplasmic RNA , as well as reverse transcription and PCR in detecting bcr / c abl mRNA of seven CML patients in various stages . ^^^ Our results showed that only a small amount of either peripheral blood or bone marrow material was required for the expression of the bcr / c abl mRNA . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Clonal analysis of bcr abl rearrangement in T lymphocytes from patients with chronic myelogenous leukemia . ^^^ The cytogenetic hallmark of chronic myelogenous leukemia ( CML ) is the Philadelphia chromosome ( Ph 1 ) , which reflects a chromosomal translocation t ( 9 ; 22 ) and a rearrangement of the ABL and bcr genes . ^^^ To address this question , we established T cell clones from peripheral venous blood cells of four patients with CML and screened these clones for bcr abl fusion transcripts by means of polymerase chain reaction and Southern blot analysis . ^^^ In four T cell clones of three of these patients , the bcr abl transcript could be detected . ^^^ None of 12 T cell clones of the fourth patient disclosed detectable bcr abl amplification product . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Molecular confirmation of BCR ABL fusion in a chronic myeloid leukemia with a complex translocation involving chromosomes 9 , 15 , and 22 . ^^^ We performed molecular studies to resolve the status of BCR and ABL in the bone marrow cells of a CML patient with a Ph chromosome resulting from a complex translocation involving chromosomes 9 , 15 , and 22 . ^^^ Furthermore , total cellular RNA isolated from the marrow was subjected to reverse transcription into cDNA and amplified by PCR with primers specific for BCR ABL fusion cDNA . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Identification of a protein that binds to the SH 3 region of Abl and is similar to Bcr and GAP rho . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Since rearrangement of ABL and BCR was shown and both genes were cloned , detection of minimal residual diseases after intensive treatment became possible at 10 ( 6 ) level using RT PCR technique . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Bcr sequences appear to activate c abl for transformation by binding to the SH 2 domain of c abl in an intramolecular interaction , presumably interfering with the adjacent SH 3 regulatory domain . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
A chimeric mRNA is formed containing sequences from a chromosome 22 gene ( bcr ) at its 5 ' end and all but the variable exon 1 of c abl sequence . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
A correction reported here to the vav sequence reveals that a central domain of some 230 amino acids is similar to the products of three genes : the human dbl oncogene , now known to encode a GDP GTP exchange factor for the Ras like polypeptide CDC42Hs ; the CDC 24 gene of Saccharomyces cerevisiae , which participates with CDC42Sc in organization of the cytoskeleton for budding ; and the human bcr gene , which recombines with the abl oncogene in certain forms of leukemia . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
On DNA level a BCR / ABL rearrangement involving the so called major BCR ( Mbcr ) from chromosome 22 has been associated with chronic myeloid leukemia ( CML ) . ^^^ Our results indicate , that heterogeneous rearrangements in bcr 2 may appear in addition to BCR / ABL rearrangements involving M bcr in Ph+CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The NarI restriction sites are very close to the BssHII sites in the BCR gene , but they differ in the ABL gene , so that NarI digests could theoretically provide additional information in chronic myeloid leukaemia ( CML ) patients . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Sequences encoded by the first exon of BCR that bind to the ABL SH 2 domain are essential for the activation of the ABL tyrosine kinase and transforming potential of the chimeric BCR ABL oncogene . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Bcr / abl recombinant DNA analysis versus karyotype in the diagnosis and therapeutic monitoring of chronic myeloid leukemia . ^^^ Karyotype and bcr / abl recombinant DNA analyses are two means of detecting the chromosomal aberration in chronic myeloid leukemia . ^^^ The authors compared these two methods in a retrospective study of 36 patients with CML in which they found the bcr / abl DNA recombinant event in 100 % ( 29 of 29 ) of those patients who had the Philadelphia chromosome . ^^^ In 76 % of the patients , bcr / abl rearrangement can be detected with a Bgl 2 digest and a 3 ' commercial probe . ^^^ By dilution studies and densitometric scanning of autoradiographs , the authors were able to detect a 15 % decrease in the relative number of cells having the bcr / abl recombinant event . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Activation of tyrosinase kinase and microfilament binding functions of c abl by bcr sequences in bcr / abl fusion proteins . ^^^ The resulting chimeric genes encode bcr / abl fusion proteins which have deregulated tyrosine kinase activity and appear to play an important role in induction of these leukemias . ^^^ A series of bcr / abl genes were constructed in which nested deletions of the bcr gene were fused to the c abl gene . ^^^ The tyrosine kinase and microfilament binding functions were not interdependent , as a kinase defective bcr / abl mutant still associated with actin filaments and a bcr / abl mutant lacking actin association still had deregulated kinase activity . ^^^ Modification of actin filament functions by the bcr / abl tyrosine kinase may be an important event in leukemogenesis . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The Philadelphia chromosome ( Ph 1 ) , detected in virtually all cases of chronic myelogenous leukemia , is formed by a reciprocal translocation between chromosomes 9 and 22 that fuses BCR encoded sequences upstream of exon 2 of c ABL . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The Philadelphia chromosome results from reciprocal translocation of genetic material between chromosome 9 and 22 involving the c abl and BCR genes respectively . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Reverse transcriptase polymerase chain reaction technique demonstrated the presence of minor bcr / abl mRNA in the former three cases , and major bcr / abl mRNA in the latter 4 cases . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The evidence that not only a BCR rearrangement but also messages of BCR / ABL fusion gene were negative made us able to differentiate this case from Ph 1 ( ) , BCR ( + ) CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Pure red cell aplasia in a case of Ph negative BCR / ABL rearranged CML with t ( 12 ; 14 ) ( q 23 ; p 11 ) . ^^^ Molecular studies by Southern and PCR analyses showed the rearrangement of the BCR and ABL sequences and expression of the chimeric bcr / abl mRNA , thus confirming the diagnosis of CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Joining of the BCR and ABL genes is an essential feature of the group of human leukemias characterized by the Philadelphia chromosome and there is recent evidence that the human BCR ABL fusion gene induces leukemia in experimental animals . ^^^ The leukemic cells of some patients carry the BCR ABL fusion gene but have an apparently normal karyotype . ^^^ Because the BCR ABL fusion gene appears to be the result of cytogenetic rearrangement in all cases of these leukemias , the causes and mechanism of chromosome rearrangement will be relevant to the development of leukemia in man . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Activation of ABL can occur by substitution of the ABL first exon with breakpoint cluster region ( BCR ) sequences or by deletion of the noncatalytic SH 3 ( src homology region 3 ) domain . ^^^ The rates of dephosphorylation of ABL and BCR ABL fusion protein by phosphotyrosine specific phosphatases are approximately the same . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BCR sequences essential for transformation by the BCR ABL oncogene bind to the ABL SH 2 regulatory domain in a non phosphotyrosine dependent manner . ^^^ BCR ABL is a chimeric oncogene implicated in the pathogenesis of Philadelphia chromosome positive human leukemias . ^^^ BCR first exon sequences specifically activate the tyrosine kinase and transforming potential of BCR ABL . ^^^ We have tested the hypothesis that activation of BCR ABL may involve direct interaction between BCR sequences and the tyrosine kinase regulatory domains of ABL . ^^^ Full length c BCR as well as BCR sequences retained in BCR ABL bind specifically to the SH 2 domain of ABL . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Strong evidence implicates fusion of control elements and 5 ' sequences of the bcr gene of chromosome 22 with 3 ' sequences of the c abl gene of chromosome 9 in the pathogenesis of Ph positive and certain cases of Ph negative chronic myelogenous leukemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We have utilized the polymerase chain reaction ( PCR ) to sensitively detect persistence of the chronic myelogenous leukemia ( CML ) malignant clone and to study bcr / abl mRNA splicing patterns following bone marrow transplantation . ^^^ In two patients bcr / abl mRNA was detected 4 and 9 months prior to clinical relapse . ^^^ Seven patients have lost all evidence of bcr / abl transcript , but only at 1 2 years posttransplant , while four have shown persistence of the bcr / abl transcript from 28 days to 3 years post BMT and one has converted from an initially negative result at 1 year post BMT to detectable levels of chimeric mRNA at 2 years . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
PCR using primers located on the translocation boundary , such as bcr and abl in CML , is very useful in the diagnosis and pursuit of the disease course . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
This an evidence of genic fusion between c abl oncogene and bcr gene and also show the possibility of rearrangement outside M bcr in these patients . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Translocation of the c abl proto oncogene from chromosome 9 to the BCR gene located on chromosome 22 produces a hybrid BCR / ABL protein resulting in chronic myelogenous leukemia . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chromosomal in situ hybridization was very informative identifying transposition of bcr and abl genes between chromosomes 22 and 9 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Entire ABL gene is joined with 5 ' BCR in some patients with Philadelphia positive leukemia . ^^^ Splicing from BCR exon 3 to ABL exon 2 crossed more than 200 kb and deleted exons 1A and 1B . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Differences in oncogenic potency but not target cell specificity distinguish the two forms of the BCR / ABL oncogene . ^^^ Two forms of activated BCR / ABL proteins , P 210 and P 185 , that differ in BCR derived sequences , are associated with Philadelphia chromosome positive leukemias . ^^^ One of these diseases is chronic myelogenous leukemia , an indolent disease arising in hematopoietic stem cells that is almost always associated with the P 210 form of BCR / ABL . ^^^ Acute lymphocytic leukemia , a more aggressive malignancy , can be associated with both forms of BCR / ABL . ^^^ While it is virtually certain that BCR / ABL plays a central role in both of these diseases , the features that determine the association of a particular form with a given disease have not been elucidated . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
DNA analysis with both conventional and pulsed field gel electrophoresis revealed the rearrangement of the c abl gene , the BCR gene outside the 5 . 8 kb breakpoint cluster region ( bcr or M BCR ) , and the comigration of an abnormal Not 1 pHabl 5 ' and 3 ' bcr fragment , indicating the presence of BCR / c abl recombination . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The 5 ' non coding region of the BCR / ABL oncogene augments its ability to stimulate the growth of immature lymphoid cells . ^^^ The Philadelphia chromosome ( Ph 1 , t 9 : 22 ; 34 : q 11 ) is a reciprocal translocation between chromosome 22 and chromosome 9 which results in the formation of the chimeric BCR / ABL oncogene . ^^^ Alternative forms of BCR / ABL are produced by splicing different sets of exons of the BCR gene to a common set of c ABL sequences . ^^^ This results in the formation of an 8 . 7 kilobase mRNA that encodes the P 210 BCR / ABL gene product or a 7 . 0 kilobase mRNA that encodes the P 185 BCR / ABL gene product . ^^^ Both BCR / ABL transcripts derive their 5 ' non coding sequences from the BCR gene locus . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The t ( 9 ; 22 ) Philadelphia chromosome translocation fuses 5 ' regulatory and coding sequences of the BCR gene to the c ABL proto oncogene . ^^^ This results in the formation of hybrid BCR ABL mRNAs and proteins . ^^^ The shift in ABL transcriptional control to the BCR promoter may play a role in cellular transformation mediated by this rearrangement . ^^^ The BCR promoter is structurally similar to the ABL promoters . ^^^ Together , this suggests that the structural fusion of BCR ABL and not its transcriptional deregulation is primarily responsible for the transforming effect of the t ( 9 ; 22 ) translocation . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In these individuals , the Ph translocation ( t ( 9 ; 22 ) ( q 34 ; q 11 ) ) results in transposition of the ABL proto oncogene from chromosome 9q34 to 22q11 , where it is fused with part of the BCR gene . ^^^ It is now known that as a result of the Ph translocation , p160BCR and p145ABL ( the normal BCR and ABL gene products ) are replaced by p210BCR ABL . ^^^ Because the Ph translocation is present in the early chronic phase , the union of the BCR and ABL genes is probably involved in the initiation of the leukaemic process . ^^^ One half of these individuals have bcr rearrangement and express p210BCR ABL . ^^^ The presence of a specific marker the BCR ABL message permits the development of new diagnostic approaches for CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Apparent decrease and elimination of BCR / ABL mRNA expressing residual cells in patients with chronic myelogenous leukemia after allogeneic bone marrow transplantation . ^^^ A modified two step polymerase chain reaction ( PCR ) was used for the amplification of BCR / ABL mRNA in 16 patients with Philadelphia chromosome positive ( Ph+ ) chronic myelogenous leukemia ( CML ) following allogeneic bone marrow transplantation ( BMT ) . ^^^ At different intervals after BMT , patient cells were assessed for the presence of BCR / ABL mRNA by two subsequent rounds of PCR amplification ; this procedure increased the sensitivity for the detection of one Ph+ cell in 10 ( 4 5 ) to one cell in 10 ( 5 6 ) . ^^^ Although five patients showed negative results by the one step PCR only , they were tested positive when nested primers were used , indicating a substantial decrease in the amount of BCR / ABL target mRNA compared with earlier pre or post transplant analyses . ^^^ Persistence of BCR / ABL mRNA expressing cells correlated with subsequent clinical relapse only when the transplantation was performed during blast crisis . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In Philadelphia chromosome ( Ph 1 ) positive chronic myeloid leukemia ( CML ) the bcr and c abl genes are reorganized and a new transcript , composed of both genes is expressed . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BCR ABL rearrangements in children with Philadelphia chromosome positive chronic myelogenous leukemia . ^^^ Leukemia cells from adults with Philadelphia ( Ph 1 ) chromosome positive chronic myelogenous leukemia ( CML ) have a characteristic molecular rearrangement between the BCR and ABL genes whereby major breakpoint cluster region ( Mbcr ) exons 2 or 3 are joined to ABL exon 2 . ^^^ Five were studied for Mbcr rearrangement using Southern blotting , nine for the presence of chimeric BCR ABL mRNA using reverse transcription and polymerase chain reaction , and three for both . ^^^ Of 12 children in whom BCR ABL mRNA was studied , 10 had Mbcr exon 2 joined to ABL exon 2 , one had Mbcr exon 3 joined to ABL 2 , and one had both Mbcr ABL junctions . ^^^ No child had BCR exon 1 joined to ABL exon 2 , the rearrangement typical of childhood Ph 1 chromosome positive acute lymphoblastic leukemia . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Clonal succession and deletion of bcr / abl sequences in chronic myelogenous leukemia with recurrent lymphoid blast crisis . ^^^ Moreover , the deletion of M bcr in recurrent BC suggests that bcr / abl may not be essential for the maintenance of cell growth in established BC . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
CML , a myeloproliferative clonal disorder of myeloid stem cells , is characterized by the consistent presence of a bcr c abl fusion gene which is formed as a result of a translocation of the c abl gene from chromosome 9 to downstream of the bcr gene on chromosome 22 ( ph ' ) . ^^^ Taking advantage of the consistent abnormal presence of the bcr c abl gene in the treated and untreated CML patients at all stages , a gene therapy at the level of blocking mRNA might be considered . ^^^ Such an antisense RNA therapy should include removal of patient ' s bone marrow , administration of the gene for constitutive expression of an antisense RNA for the bcr c abl fusion gene into the myeloid stem cells and reinjecting the engineered marrow into the patient . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The Philadelphia 1 ( Ph 1 ) chromosome results from a reciprocal translocation between chromosome 9 and chromosome 22 , which fuses a portion of the ABL oncogene to the BCR gene , forming the BCR / ABL fusion gene . ^^^ The BCR / ABL gene is transcribed from the promoter of the normal BCR gene , but little is known about the regulation of its expression . ^^^ Sequence specific DBP located within the Mbcr could have a transcription regulating effect , and they could participate in the recombination that generates BCR / ABL . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The molecular genetics of the Philadelphia ( Ph 1 ) chromosome , arising from a reciprocal translocation between chromosomes 9 and 22 and involving the genes abl and bcr , has been well characterized . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Eight patients with Ph+AL were studied with pulsed field gel electrophoresis ( PFGE ) to examine the break site within ABL and BCR genes . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
None of the 13 investigated BCR patients had detectable BCR / ABL transcripts using polymerase chain reaction ( PCR ) and none had an N RAS mutation . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The characteristic genetic exchange in chronic myeloid leukemia ( CML ) is the fusion of the ABL proto oncogene and a specific part of the BCR or phl gene . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In three of these cases , a complete cytogenetic response was confirmed at the DNA level by Southern blotting , but specific amplification of the BCR / ABL junction by the polymerase chain reaction ( PCR ) , performed in two cases , still showed residual disease . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
This gene fusion between c abl oncogene and bcr gene is typical of the Ph chromosome . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The translocation between chromosome 9 and chromosome 22 which creates the Philadelphia chromosome moves the ABL oncogene from its normal location on chromosome 9 and fuses it with a portion of the BCR gene on chromosome 22 . ^^^ This new BCR / ABL fusion gene generates a unique 8 . 7 kilobase ( kb ) RNA which codes for a new 210 kilodalton ( kd , p 210 ) protein which has a protein tyrosine kinase activity that is greatly increased in comparison to the normal ABL protein . ^^^ The human K 562 cell line was derived from a patient with CML , and serves as one model for the regulation of expression of the ABL and BCR / ABL genes . ^^^ This study examines the expression of the BCR / ABL fusion gene and the normal ABL gene in relation to differentiation and changes in proliferative state . ^^^ The expression of both the normal ABL transcripts and the BCR / ABL fusion transcript decrease approximately ten fold when the cells are induced to differentiate with hemin . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BCR first exon sequences specifically activate the BCR / ABL tyrosine kinase oncogene of Philadelphia chromosome positive human leukemias . ^^^ In contrast , the human BCR / ABL oncogene of the Philadelphia chromosome translocation has an intact SH 3 domain and its product is not myristylated at the N terminus . ^^^ To analyze the contribution of BCR encoded sequences to BCR / ABL mediated transformation , the effects of a series of deletions and substitutions were assessed in fibroblast and hematopoietic cell transformation assays . ^^^ BCR first exon sequences specifically potentiate transformation and tyrosine kinase activation when they are fused to the second exon of otherwise intact c ABL . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
P 210 BCR ABL is complexed to P 160 BCR and ph P 53 proteins in K 562 cells . ^^^ Cells containing the Ph 1 contain a chimeric gene formed from the fusion of BCR ( Collins et al . , 1987 ; Lifshitz et al . 1988 ) and ABL genes that results from the reciprocal translocation of segments of chromosomes 9 and 22 ( Shtivelman et al . , 1985 ) . ^^^ The product of this chimera is a 210 kDa protein , termed P 210 BCR ABL , that possesses an activated tyrosine kinase activity ( Konopka et al . , 1984 ; Kloetzer et al . , 1985 ) . ^^^ Studies using long term marrow culture systems and retrovirus mediated gene transfer have documented that P 210 BCR ABL can stimulate the growth of immature hematopoietic precursor cell types ( McLaughlin et al . , 1987 ; Young & Witte , 1984 ) . ^^^ We have previously reported that P 210 BCR ABL exists in cytoplasmic complexes in association with a 53 kDa protein termed ph P 53 ( Maxwell et al . , 1987 ; Li et al . 1988 ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Philadelphia chromosome positive chronic myelogenous leukemia with deleted fusion of BCR and ABL genes . ^^^ In the great majority of patients with chronic myelogenous leukemia ( CML ) the reciprocal translocation between chromosomes 9 and 22 , t ( 9 ; 22 ) ( q 34 ; q 11 ) , resulting in the Philadelphia ( Ph ) chromosome produces fusion DNA sequences consisting of the 5 ' part of the major breakpoint cluster region 1 ( M BCR 1 ) and the ABL protooncogene which encodes for the P210BCR ABL phosphoprotein with tyrosine kinase activity implicated in the pathogenesis of CML . ^^^ Molecular analysis was performed on 25 patients with Ph positive CML using 2 breakpoint cluster region ( bcr ) probes within the M BCR 1 DNA sequences , and two of them did not contain either detectable rearranged DNA homologous to the 5 ' side bcr probe or ABL related fusion mRNA . ^^^ The chromosomal in situ hybridization technique revealed that these two Ph positive CML cases did not carry DNAs homologous to the 5 ' bcr or ABL probes on the Ph chromosome . ^^^ Thus , the possibility is raised that the BCR / ABL fusion DNA has been deleted in rare CML cases , and that the deletion possibly occurred in a stepwise manner following the formation of the Ph chromosome at any stage of the disease . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In Philadelphia chromosome positive chronic myeloid leukemia and acute lymphocytic leukemia cells the bcr and c abl genes are reorganized and transcripts composed of both genes are expressed . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
This case illustrates the extensive and complex types of genetic alteration that may be associated with a c abl and bcr fusion . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Ph negative chronic myeloid leukemia : molecular analysis of ABL insertion into M BCR on chromosome 22 . ^^^ M BCR was rearranged and chromosome in situ hybridization showed an ABL insertion between 5 ' and 3 ' M BCR on an apparently normal chromosome 22 . ^^^ The association of 5 ' BCR and 3 ' ABL at the 5 ' junction of the chromosome 9 insert was typical of that found for the BCR ABL fusion gene in other patients with the standard t ( 9 ; 22 ) and CML . ^^^ Field inversion gel electrophoresis and chromosome in situ hybridization studies using a probe isolated from genomic DNA 5 ' of the junction showed that 3 ' M BCR was joined to a region of chromosome 9q34 rich in repetitive sequences and lying some distance 3 ' of ABL . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Acute leukaemia in bcr / abl transgenic mice . ^^^ The Philadelphia chromosome , widely implicated in human leukaemia , is the result of a reciprocal translocation t ( 9 ; 22 ) ( q 34 ; q 11 ) in which the abl oncogene located at 9q34 is translocated to chromosome 22q11 , where it is fused head to tail with 5 ' exons of the bcr gene . ^^^ This second type of translocation results in the transcription of a 7 . 0 kilobase chimaeric bcr / abl messenger RNA translated into a bcr / abl fusion protein , p 190 , which has an abnormal tyrosine kinase activity and is strongly autophosphorylated in vitro . ^^^ We have generated mice transgenic for a bcr / abl p 190 DNA construct and find that progeny are either moribund with , or die of acute leukaemia ( myeloid or lymphoid ) 10 58 days after birth . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Nevertheless , bcr rearrangement and expression of the classic bcr / abl chimeric mRNA was found in only 1 of the 6 patients . ^^^ It was investigated whether Ph CML with clinical and morphological features indicating true CML would always have bcr rearrangements , as the relocation of c abl from 9q34 into the breakpoint cluster region on 22q11 is considered a crucial event in the pathogenesis of CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In the majority of Philadelphia ( Ph ) positive chronic myeloid leukemia ( CML ) patients , the c abl gene is fused to the bcr gene , resulting in the transcription of an 8 . 5 kb chimeric bcr abl mRNA , which is translated into a p210bcr abl fusion protein . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The role of alternative splicing patterns of BCR / ABL transcripts in the generation of the blast crisis of chronic myeloid leukaemia . ^^^ In addition , alternative splicing of the mRNA transcribed from the BCR / ABL fusion gene has been reported and it has been suggested that this may play a role in the generation of the acute phase of Philadelphia positive chronic myeloid leukaemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
New type of Bcr / Abl junction in Philadelphia chromosome positive chronic myelogenous leukemia . ^^^ A new and rare type of Bcr / Abl junction between exon C 3 of the 3 ' portion of the Bcr gene and Abl exon 2 has been identified in the leukemic cells of two Ph 1 positive chronic myelogenous leukemia patients in chronic phase . ^^^ This is the fourth type of Bcr / Abl junction so far identified in Ph 1 positive hematologic malignancies and is a consequence of an unusual breakpoint position on chromosome 22 that falls approximately 20 kb downstream of the major breakpoint cluster region ( bcr ) of the Bcr gene . ^^^ The new hybrid mRNA is 540 base pairs ( bp ) longer than that expressed by the K 562 cell line and could codify for a Bcr / Abl protein carrying 180 additional aminoacids with respect to the larger P 210 protein so far identified . ^^^ The hematologic phenotype expressed by the two patients carrying this unusual type of Bcr / Abl rearrangement does not significantly differ from that commonly seen in chronic myelogenous leukemia . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Molecular studies in two cases revealed neither a BCR rearrangement nor a translocation of the ABL protooncogene , as observed in Ph 1 positive chronic myeloid leukemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BCR ABL and BCR proteins : biochemical characterization and localization . ^^^ The Philadelphia translocation results in the expression of a family of chimaeric proteins in which a portion of the bcr protein is fused to c abl protein . ^^^ Using antibodies which recognize different portions of the bcr gene and abl gene products we have compared the normal bcr products with their chimaeric counterparts . ^^^ We first conclude that the enhanced kinase activity of the rearranged bcr abl products ( p 210 and p 190 ) is recovered almost exclusively from the cytosolic fraction . ^^^ To determine whether the distribution of kinase activity reflected the bulk distribution of the bcr abl proteins , in vivo labeling followed by subcellular fractionation was performed . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
P 190 BCR / ABL transcript in a case of Philadelphia positive multiple myeloma . ^^^ No rearrangement was observed within the major breakpoint cluster region ( M BCR ) although she was found to have a P 190 BCR / ABL hybrid transcript using PCR . ^^^ Philadelphia positive multiple myeloma is a very rare event and , so far , no molecular data about the involvement of the BCR and C ABL genes are available . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Detection of bcr abl fusion in chronic myelogeneous leukemia by in situ hybridization . ^^^ Chronic myelogeneous leukemia ( CML ) is genetically characterized by fusion of the bcr and abl genes on chromosomes 22 and 9 , respectively . ^^^ Two color fluorescence in situ hybridization ( FISH ) was used with probes from portions of the bcr and abl genes to detect the bcr abl fusion in individual blood and bone marrow cells from six patients . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The promoter of the human BCR gene , regulating the transcription of the chimeric BCR / ABL mRNA in leukemia , has been isolated and characterized . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Application of cosmid probes for 3 ' ABL and 5 ' BCR sequences gave better results than libraries for chromosomes 9 and 22 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chromatin alterations surrounding the BCR / ABL fusion gene in K 562 cells . ^^^ Chronic myelogenous leukemia ( CML ) is characterized by the presence of a novel fusion gene comprised of portions of the BCR gene from chromosome ( ch ) 22 and the ABL gene from ch 9 . ^^^ We identify five hypersensitive ( HS ) sites within the abnormal BCR / ABL allele in K 562 cells in a pattern different from the normal BCR . ^^^ These results indicate that the normal BCR has a chromatin configuration consistent with active transcription and that the BCR / ABL fusion gene chromatin is different . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Pulsed field gel electrophoretic analysis demonstrated the comigration of both ABL and BCR sequences on the same BssHII and SacII fragment . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Thus , the results demonstrate the presence of a c abl / bcr rearrangement in the masked Ph corresponding to that observed in the standard Ph translocation t ( 9 ; 22 ) ( q 34 ; q 11 ) of CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Absence of bcr rearrangement and bcr / abl RNA in a patient with a 31 year survival of CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Cytogenetic and molecular analysis during this second chronic phase confirm the presence of the Philadelphia chromosome and its transcribed BCR ABL mRNA . ^^^ The breakpoint within M bcr occurred in the 3 ' portion of the region and expressed a hybrid joining the b 3 exon of BCR to the a 2 exon of ABL . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
None of the patient showed breakpoint cluster region ( BCR ) gene rearrangement by Southern blot analysis , however , PCR technique revealed the bcr / abl mRNA in 13 of 24 patients . ^^^ In patients who received CY + TBI as a conditioning regimen , 6 out of 8 patients were detected bcr / abl mRNA by PCR . ^^^ On the other hand , patients who received high dose AraC+ CY + TBI or busulfan + CY as a conditioning , bcr / abl mRNA was detected in 4 out of 9 patients and 1 out of 5 patients , respectively . ^^^ There was no clear association between the presence or absence of graft versus host disease and the detection of bcr / abl mRNA by PCR . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The hallmarks of chronic myelogenous leukemia ( CML ) include the Philadelphia chromosome ( Ph ) translocation [ t ( 9 ; 22 ) ( q 34 ; q 11 ) ] and consistent molecular genetic aberrations : a break within a restricted 5 . 8 kb DNA segment , bcr , on chromosome 22q11 ; transposition of the c abl protooncogene from chromosome 9q34 to 22q11 ; and formation of a hybrid bar abl gene encoding an abnormal 210 Kd bcr abl protein with augmented tyrosine kinase enzymatic activity . ^^^ Our current observations suggest that a chronic myeloid leukemia process can develop without associated changes in the bcr or c abl genes . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The molecular dissection of the Philadelphia chromosome has revealed that this translocation activates the c abl oncogene by fusion with another gene called bcr whose function is as yet unknown . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Molecular abnormalities of bcr and c abl in chronic myelogenous leukemia associated with a long chronic phase . ^^^ Since molecular abnormalities of bcr and c abl occur in CML , we sought to determine whether there were differences in bcr and c abl translocation or transcription in individuals with long 5 short chronic phase . ^^^ All patients had translocation of c abl to within bcr . ^^^ Transcription of the chimeric bcr / c abl mRNA was comparable . ^^^ These data suggest that changes in bcr or c abl alone do not determine the duration of chronic phase in CML ; other factors are likely involved . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Detection of minimal residual bcr / abl transcripts by a modified polymerase chain reaction . ^^^ The fused bcr / abl gene is transcribed into two types of chimeric mRNA . ^^^ By means of a combined method of S 1 nuclease protection and polymerase chain reaction , we amplified sequences representative of the chimeric bcr / abl transcripts . ^^^ Only 5 micrograms of total cellular RNA is needed and the chimeric bcr / abl message can be detected at a dilution of 1 : 100 , 000 . ^^^ We also detected residual chimeric bcr / abl transcripts in the remission samples from two Ph 1 positive CML patients . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Antibody recognition of the tumor specific bcr abl joining region in chronic myeloid leukemia . ^^^ Due to this translocation , the abl oncogene is coupled to the bcr gene , forming a new determinant in this protein encoded by the bcr abl joining region . ^^^ In the joining region itself , either the bcr exon 2 is coupled to the abl exon 2 ( b 2 a2 ) , or the bcr exon 3 is coupled to the abl exon 2 ( b 3 a2 ) . ^^^ Thus , these joining regions form by definition new tumor specific determinants in the respective chimeric P 210 bcr abl molecules . ^^^ In this context , the bcr abl junctions were first analyzed at the DNA and RNA level . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Tyrosine kinase activity and transformation potency of bcr abl oncogene products . ^^^ Oncogenic activation of the proto oncogene c abl in human leukemias occurs as a result of the addition of exons from the gene bcr and truncation of the first abl exon . ^^^ Analysis of tyrosine kinase activity and quantitative measurement of transformation potency in a single step assay indicate that variation in bcr exon contribution results in a functional difference between p210bcr abl and p185bcr abl proteins . ^^^ Thus , foreign upstream sequences are important in the deregulation of the kinase activity of the abl product , and the extent of deregulation correlates with the pathological effects of the bcr abl proteins . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In both instances a chimeric gene , formed between bcr and the abl protooncogene , results in expression of fused bcr abl proteins with tyrosine kinase activity . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic myelogenous leukemia ( CML ) is associated with the reciprocal translocation of a region of chromosome 22 called BCR with the c abl gene of chromosome 9 . 5 ' coding sequences from the BCR gene are spliced in frame to the second exon of the ABL gene to produce a CML specific 8 . 5 kilobase message which encodes the BCR ABL hybrid protein P 210 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
After molecular evaluation using in situ hybridization and Southern blotting techniques , the involvement of the altered bcr / abl gene was demonstrated and the cytogenetic analysis was revised . ^^^ Utilization of molecular probes in the evaluation of such cases should become a routine diagnostic procedure in detecting the exchange of bcr and c abl sequences . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The t ( 9 ; 22 ) generating the Ph 1 chromosome in CML creates a new fusion gene ( bcr / abl ) , which combines bcr sequence from chromosome 22 with abl sequence from chromosome 9 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
These data support the notion that the unusual genetic recombinations that give rise to BCR / ABL fusion genes in CML involve specific DNA sequences of BCR ( and possibly ABL ) and additional , recombinogenic sequences , at least some of which are present in loci known to be nonrandomly involved in complex Ph 1 translocations . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Analysis of BCR ABL mRNA in chronic myelogenous leukemia patients and identification of a new BCR related sequence in human DNA . ^^^ The major consequence of the aberration is the fusion of the ABL and BCR genes . ^^^ We have used the polymerase chain reaction ( PCR ) to detect these mRNAs in 53 patients and cell lines and found that around 20 % contain simultaneously two BCR ABL mRNAs , presumably due to a process of alternative splicing . ^^^ The results also indicate that most patients in lymphocytic blast crisis of CML contain the mRNA in which bcr exon 2 is linked to ABL exon 2 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The blasts had a normal 46XX karyotype and showed no fusion of the bcr and abl genes associated with Philadelphia chromosome positive leukemia . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The interest of the study was strengthened by the fact that 1 ( 17q ) is frequently seen in CML and by recent reports showing that genomic changes of c abl and bcr genes can be present even in the absence of a Ph chromosome . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic myeloid leukemia ( CML ) is characterized by the Philadelphia chromosome which results from a reciprocal ( 9 ; 22 ) translocation , with the protooncogene c abl moving from chromosome 9 to 22 and juxtaposed to the proximal bcr . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The Ph chromosome is the result of a reciprocal translocation between chromosomes 9 and 22 and involves the ABL and BCR genes resulting in a chimeric mRNA encoding a specific protein , termed P 210 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Studies of BCR and ABL gene rearrangements in chronic myelogenous leukemia patients by conventional and pulsed field gel electrophoresis using gel inserts . ^^^ Because the Ph chromosome has been characterized molecularly to involve a reciprocal translocation between the ABL and BCR genes , there is an increasing interest in the use of molecular probes to detect chromosomal rearrangements in this disease . ^^^ While rearrangements involving the bcr region of the BCR gene can be detected by conventional gel electrophoresis ( CGE ) , detection of those involving ABL generally requires pulsed field gel electrophoresis ( PFGE ) . ^^^ The advantages of this method are demonstrated by studying both bcr and ABL rearrangements in bone marrow and peripheral blood samples of CML patients . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Structural alterations of the BCR and ABL genes in Ph 1 positive acute leukemias with rearrangements in the BCR gene first intron : further evidence implicating Alu sequences in the chromosome translocation . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Mutations of the ras protooncogenes in chronic myelogenous leukemia : a high frequency of ras mutations in bcr / abl rearrangement negative chronic myelogenous leukemia . ^^^ Aberrant ras genes were detected in none of 39 patients with Philadelphia ( Ph ) chromosome or bcr / abl rearrangement positive chronic phase CML and in only 1 of 18 patients in blast crisis , suggesting that ras mutations have little or no role in initiation or progression of common CML . ^^^ Seven of 13 , or 54 % of patients with bcr / abl rearrangement negative chronic phase CML ( atypical CML ) harbored mutations in ras , however . ^^^ This high incidence of ras mutations , together with the absence of bcr / abl rearrangement , provides evidence that atypical CML is an entity that is molecularly distinct from common CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
As a consequence of the translocation , the Abelson protooncogene ( ABL ) , located on chromosome 9 is moved to chromosome 22 where it is joined to a truncated gene , known as BCR . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Blast phase chronic myeloid leukaemia was excluded by lack of involvement of the ABL and BCR genes . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Philadelphia positive chronic myelogenous leukemia with typical bcr / abl molecular features and atypical , prolonged survival . ^^^ In most patients in fact the bcr / abl rearrangements are identical both in chronic phase and in blast crisis , and overall differences in chronic phase duration , related to different location of breakpoints inside the bcr region , were found to be marginal . ^^^ We approached this problem by studying the molecular features of the bcr / abl abnormality in rare CML patients with very long , atypical chronic phase . ^^^ The three patients studied , whose chronic phase duration is 17 , 19 , and 21 years , respectively , have typical genomic bcr rearrangements , and two of them show , hybridizing Northern blots to c abl , the 8 . 5 kb mRNA , as that typically present in CML . ^^^ It seems that genomic alterations within bcr and abl can not account , alone , for the duration of the chronic phase of Ph 1 positive CML and those quantitative and / or qualitative alterations of the p 210 bcr / abl protein , unluckily awkward to prove , might be responsible for the atypical clinical features of these CML long survivors . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Alternative forms of the BCR ABL oncogene have quantitatively different potencies for stimulation of immature lymphoid cells . ^^^ Alternative chimeric oncogenes are formed by splicing different sets of BCR gene exons on chromosome 22 across the translocation breakpoint to a common set of ABL oncogene sequences on chromosome 9 . ^^^ This results in an 8 . 7 kilobase mRNA that encodes the P 210 BCR ABL gene product commonly found in patients with chronic myelogenous leukemia or a 7 . 0 kilobase mRNA that produces the P 185 BCR ABL gene product found in most Philadelphia chromosome positive patients with acute lymphocytic leukemia . ^^^ Structural changes in BCR may regulate the effectiveness of the ABL tyrosine kinase function , as monitored by lymphocyte growth response . ^^^ Changes in mitogenic potency may help to explain the more acute leukemic presentation usually associated with expression of the P 185 BCR ABL oncogene . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Rearrangement of the breakpoint cluster region ( bcr ) and the chromosomal location of c abl and 3 ' bcr were studied in two patients with Philadelphia chromosome ( Ph 1 ) negative chronic myelocytic leukemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
CML T 1 cells exhibit molecular changes typical of CML , including translocation of the ABL protooncogene from chromosome 9 to 22 , rearrangement of the BCR gene , and transcription of a chimeric BCR ABL messenger RNA ( mRNA ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In chronic myeloid leukemia and some cases of acute lymphoblastic leukemia , a 9 ; 22 chromosome translocation has fused most of the c abl oncogene to a gene designated bcr . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The chromosome 9 ABL sequence around the breakpoint shows homology to the consensus Alu sequence whereas the chromosome 22 BCR sequence does not . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Fused transcript of abl and bcr genes in chronic myelogenous leukaemia . ^^^ Human chronic myelogenous leukaemia is characterized by a reciprocal translocation between chromosomes 9 and 22 resulting in an abbreviated form of chromosome 22 and the transfer of the abl cellular oncogene from chromosome 9 into the bcr gene of chromosome 22 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Heterogeneity of genomic fusion of BCR and ABL in Philadelphia chromosome positive acute lymphoblastic leukemia . ^^^ We demonstrate a BCR ABL fusion gene on the Philadelphia chromosome . ^^^ The breakpoint on chromosome 9 is within ABL between exons Ia and 2 , and the breakpoint on chromosome 22 is approximately equal to 50 kilobases upstream of a breakpoint cluster region in an intron of the BCR gene . ^^^ This upstream BCR breakpoint leads to inclusion of fewer BCR sequences in the fusion gene , compared with the BCR ABL fusion gene of chronic myelogenous leukemia . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In the four cases studied the c abl proto oncogene was translocated to chromosome 22 and in five cases there was transcription of a chimeric bcr abl mRNA . ^^^ Factors other than the bcr / c abl rearrangement must underlie the clinical heterogeneity of CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The aberrant abl protein product of a chronic myelogenous leukemia ( CML ) blast crisis cell line ( K 562 ) and of five Philadelphia chromosome positive CML patients in blast crisis were analyzed by an immune complex kinase assay using two antipeptide sera generated against the hydrophilic domain of 5 abl and a region within the third exon of the breakpoint cluster region ( bcr ) respectively . ^^^ Both the anti abl and anti bcr sera detected a 210 kd band in extracts derived from K 562 cells and from two CML patients with myeloid blast crisis . p 210 was detected by the anti abl but not the anti bcr sera in three CML patients with myeloid ( one patient ) and lymphoid ( two patients ) blast crisis , indicating the absence of bcr exon 3 in this protein . ^^^ Our observations demonstrate that the Philadelphia translocation results in the generation of a chimeric bcr abl protein with at least two molecular variants , both of which are enzymatically active as protein kinases . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Alternative splicing of RNAs transcribed from the human abl gene and from the bcr abl fused gene . ^^^ In the human cell line K 562 , abl is translocated from chromosome 9 to within the bcr gene on chromosome 22 . ^^^ Within the fused bcr abl gene , abl exon 2 alternatively splices to two adjacent bcr exons . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Using bcr cDNA sequences , we obtained data strongly suggesting the presence of a chimaeric bcr / abl mRNA in the leukaemic cells of Ph ' positive CML patients . ^^^ The recent isolation of cDNA clones containing bcr and abl sequences confirms this finding . ^^^ Because the bcr part of the chimaeric mRNA could be required to induce the transforming activity of the human c abl oncogene , we have now initiated studies to characterize the normal ' bcr gene ' and to determine the effect of a translocation within its coding domain . ^^^ We demonstrate that as a result of the Ph ' translocation , a variable number of bcr exons are included in the chimaeric bcr / abl mRNA . ^^^ The bcr gene sequences in this mRNA could be responsible for the transition of the abl cellular proto oncogene into an oncogene . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Additional c abl / bcr rearrangements in a CML patient exhibiting two ph 1 chromosomes during blast crisis . ^^^ Recent data suggest that two human genes , c abl on chromosome 9 and bcr on chromosome 22 , are involved in the generation of Ph 1 positive CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
This translocation relocates the proto oncogene c abl , normally found on chromosome 9q34 , to within the breakpoint cluster region ( bcr ) on chromosome 22q11 ( refs 3 8 ) . ^^^ The juxtaposition of c abl and the 5 ' portion of bcr appears to be the critical genomic event in CML and results in a novel 8 kilobase ( kb ) fused abl / bcr transcript and a c abl related protein of relative molecular mass 210 , 000 ( ref . 11 ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
No rearrangements could be demonstrated within or near the genes c myc , c myb , c abl , bcr , c Ki ras , and N ras . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
This translocation creates a chimeric gene composed of breakpoint cluster region ( bcr ) sequences from chromosome 22 fused to a portion of the abl oncogene on chromosome 9 . ^^^ Protein expression is not related to amplification of the abl gene but to variation in the level of bcr abl mRNA produced from a single Ph 1 template . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The chronic myelocytic cell line K 562 contains a breakpoint in bcr and produces a chimeric bcr / c abl transcript . ^^^ Employing K 562 , we demonstrate the presence of an abnormally sized mRNA species hybridizing to c abl and to a bcr cDNA probe , indicating the possible consequence of the Ph 1 translocation on a transcriptional level in chronic myelocytic leukemia . ^^^ Cloning of large stretches of chromosomal DNA flanking bcr and c abl sequences in K 562 and identification of the exons participating in the formation of the chimeric mRNA shows that a splice of at least 99 kilobases is made to fuse the 3 ' bcr exon to the 5 ' c abl exon . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The c abl protooncogene is translocated from chromosome 9 band q 34 into bcr and the biochemical consequence of this molecular rearrangement is the production of an abnormal fusion protein bcr abl p 210 with enhanced protein tyrosine kinase activity compared to the normal p 145 c abl protein . ^^^ We present evidence that the Ph+ , bcr leukaemias are associated with a novel p 190 abl kinase . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The Ph 1 chromosome results from the fusion of c abl proto oncogene sequences from chromosome 9 to phl gene sequence on chromosome 22 . ( The phl gene is often referred to as bcr . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
At a molecular level , the Ph ' has recently been shown to represent the translocation of c abl to a limited ( breakpoint cluster region , bcr ) on chromosome 22 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The c abl , bcr and C lambda genes are amplified in a cell line but not in the uncultured cells from a patient with chronic myelogenous leukemia . ^^^ We report that the c abl , bcr , and C lambda genes are amplified approximately eight fold in the cell line but not in the fresh uncultured cells from which KBM 5 was derived . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The major consequence of the formation of the Philadelphia ( Ph 1 ) chromosome characteristic of leukemia cells of patients with chronic myelogenous leukemia ( CML ) is fusion of c abl and bcr genes . ^^^ In most , we identified one or both species of bcr abl chimeric transcripts . ^^^ These two mRNAs vary in the specific bcr exon joined to abl exon 2 and are translated into slightly different proteins . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The leukemic cells isolated from a patient with CML in myeloid crisis contained a novel 8 kilobase ( kb ) abl related messenger RNA ( mRNA ) , but the TOM 1 cells contained c abl transcripts of only normal sizes , despite the fact that they showed the bcr gene rearrangement . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
DNA sequence for human bcr , the gene that translocates to the abl oncogene in chronic myeloid leukaemia . ^^^ The hallmark of human chronic myeloid leukaemia is a 9 ; 22 chromosome translocation that fuses most of the c abl oncogene to the 5 ' portion of the breakpoint cluster region ( bcr ) gene , such that a hybrid bcr abl mRNA and polypeptide are generated . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The BCR 2 and BCR 4 loci are amplified in leukemia cell line K 562 cells , indicating that they fall within the amplification unit that includes immunoglobulin lambda light chain locus ( IGL ) and ABL locus on the K 562 Philadelphia chromosome ( Ph 1 ) ; additionally , in chronic myelogenous leukemia derived mouse human hybrids retaining a Ph 1 chromosome in the absence of the 9q+ and normal chromosome 22 , BCR 2 and BCR 4 loci are retained , whereas the 3 ' region of BCR 1 and the BCR 3 locus are lost , indicating that BCR 3 is distal to BCR 1 on chromosome 22 . ^^^ Thus , the order of loci on chromosome 22 is centromere BCR 2 , BCR 4 , and IGL BCR 1 BCR 3 SIS , possibly eliminating BCR 2 and BCR 4 loci as candidate targets for juxtaposition to the ABL gene in the acute lymphoblastic leukemia Ph 1 chromosome . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Although in situ hybridization of 5 abl proved , and restriction endonuclease analyses of the bcr region strongly indicated the occurrence of bcr abl rearrangement in PB 1049 and PB 1049 T , we could not obtain any evidence for the expression of the hybrid bcr abl mRNA . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Significance of the Philadelphia chromosome in acute leukemias : variable correlation with rearrangements involving the c abl and bcr genes . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
By combining a variety of cDNA cloning techniques , we have isolated bcr / abl clones representing 8 . 7 kb of contiguous mRNA sequence . . ^^^ This translocation fuses sequences from a variable distance 5 ' to the c abl locus on chromosome 9 to sequences in a breakpoint cluster region ( bcr ) on chromosome 22 . ^^^ The appearance of the Ph 1 chromosome is correlated with the production of a novel 8 . 7 kb RNA transcript containing both bcr and c abl sequences as well as with a 210 kd phosphoprotein ( p210c abl ) representing non abl polypeptide sequences fused to c abl derived sequences . ^^^ Antibodies prepared to a number of different c abl domains and to bcr determinants were employed to characterize the normal and altered c abl gene products . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Leukemic cells from patients with Philadelphia chromosome ( Ph 1 ) positive chronic myelogenous leukemia ( CML ) contain a 210 kDa protein ( P210bcr abl ) with a protein tyrosine kinase activity that is a product of fused bcr and abl genes . ^^^ Several different anti abl and anti bcr antibodies detected the ph P53 / P210 complex . ^^^ Our results indicate that ph P 53 is not a degraded product of P210bcr abl , does not share antigenic determinants with P210bcr abl since it is not recognized by anti abl and bcr antibodies in immunoblots , is not the phosphorylated heavy chain of immunoglobulin G , and is different from p 53 ( the nonviral T protein ) complexed to the large T antigen of simian virus 40 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In situ hybridization with c abl and bcr probes showed that a 3 ' bcr sequence was translocated to the der ( 8 ) chromosome , while the c abl oncogene was transposed to the masked Ph . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Her cells were Ph negative , but hybridization of gene probes to chromosomes in situ and to leukaemic DNA showed that the abl oncogene had moved to the breakpoint cluster region ( bcr ) on the normal chromosome 22 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In situ hybridization studies showed transposition of the abl gene from chromosome 9q34 to the breakpoint cluster region ( bcr ) of chromosome 22 in all five patients ; this was confirmed by rearrangements of the bcr gene in leukemic DNA . ^^^ These results confirm that association of abl and bcr is a consistent feature of chronic myeloid leukemia irrespective of the cytogenetic presentation and support the conclusion of Hagemeijer that all simple variant Ph translocations are , in fact , complex and involve at least three chromosomes . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Considerable complexity exists in the types of genetic changes that can juxtapose bcr and the c abl oncogene in CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Philadelphia chromosome positive leukemia : molecular analysis of bcr and abl genes and transforming genes . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
There was no bcr abl chimeric mRNA typical of Ph positive chronic myeloid leukemia ( CML ) . ^^^ Leukemic cell metaphases were studied by the technique of in situ hybridization with probes for C lambda , sis , abl , and 5 ' bcr . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
This data indicates an important role for abl and bcr and suggest some common mechanisms of activation of c abl related tyrosine kinase activity . ^^^ Finally , this data reviewed suggests that factors other than abl and bcr must play a role in CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Furthermore , c abl and bcr genes might play some role in maintaining the spatial relationship . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The Philadelphia translocation , t ( 9 ; 22 ) , fuses the BCR and ABL genes resulting in the expression of leukemia specific , chimeric BCR ABL messenger RNAs . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
CML is characterized by the t ( 9 : 22 ) chromosome translocation which results in translocation of the oncogene abl from chromosome 9 into the breakpoint cluster region ( bcr ) gene on chromosome 22 . ^^^ The latter as well as 902 or 927 amino acids are included within the CML specific bcr abl mRNA transcribed from the chimeric bcr abl gene on chromosome 22 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In chronic myelocytic leukemia , the human c abl oncogene is translocated from chromosome 9 to a region on chromosome 22 designated as the breakpoint cluster region ( bcr ) ( A . de Klein , A . ^^^ The abnormal mRNA represents a chimeric transcript consisting of 5 ' bcr and 3 ' c abl sequences ( G . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In the CML specific ( 9 ; 22 ) translocation the transposition of the c abl oncogene to the chromosome 22 bcr sequences results in the production of a chimeric bcr / c abl fusion protein . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
A complete open reading frame initiating in sequences of the bcr gene and reading through the abl oncogene segment has been determined . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Recently , molecular investigations of Ph positive CML cases have revealed a consistent genomic recombination between two genes , BCR on chromosome 22 and the ABL oncogene . ^^^ This molecular rearrangement expresses a unique 8 . 5 kb BCR ABL hybrid mRNA transcript , that encodes an altered BCR ABL protein of approximately 210 kD with enhanced in vitro tyrosine kinase activity . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The BCR / ABL hybrid gene . ^^^ The remaining BCR sequences act as an acceptor for a chromosome 9 gene , the ABL oncogene : the ABL oncogene is fused in a head to tail fashion to the chromosome 22 sequences . ^^^ This genomic configuration results in the transcription of a novel chimeric mRNA consisting of 5 ' BCR sequences and 3 ' ABL oncogene sequences . ^^^ In K 562 , a cell line derived from a CML patient , and in five CML patients such chimeric BCR / ABL transcripts have been demonstrated . ^^^ The role of the BCR part of the fusion protein is unknown ; it is possible that the BCR moiety could alter the structure of the ABL protein and unmask its tyrosine kinase activity . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Molecular studies of bcr gene configuration and c abl transcription allowed two groups of Ph1+ ANLL to be distinguished . ^^^ Three cases had bcr rearrangement and c abl mRNA expression comparable to those reported in Ph1+ chronic myeloid leukemia , while three others had not detectable bcr rearrangement and a 7 . 2 7 . 5 kb c abl mRNA . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Rearrangement of the c abl and bcr genes in Ph negative CML and Ph positive acute leukemias . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The Philadelphia chromosome ( Ph 1 ) of chronic myelogenous leukemia ( CML ) contains sequences from chromosome 9 , including the ABL protooncogene , that have been translocated to the breakpoint cluster region ( bcr ) of chromosome 22 , giving rise to a bcr ABL fusion gene , whose product has been implicated in the genesis of CML . ^^^ Although chromosome 22 translocation breakpoints in CML virtually always occur within the 5 . 8 kilobase ( kb ) bcr , chromosome 9 breakpoints have been identified within the known limits of ABL in only a few instances . ^^^ The chromosome 9 breakpoint was shown to have occurred within an ABL intron , 160 kb upstream of the 5 abl homologous sequences , but still 35 kb downstream of the 5 ' most ABL exon . bcr ABL and ABL bcr fusion genes were demonstrated on the Ph 1 and the 9q+ chromosomes , respectively ; both of these genes are expressed . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In K 562 cells , amplified and rearranged c abl genes show a pattern of temporal replication during S that is similar to the pattern observed for the 5 ' breakpoint cluster region ( bcr ) and the amplified C lambda light chain immunoglobulin genes . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
At a molecular level the first two patients showed the same juxtaposition of c abl and bcr genes as is seen in Ph positive CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In chronic myelogenous leukemia ( CML ) the reciprocal translocation resulting in the Philadelphia chromosome ( Ph 1 ) leads to the formation of a chimeric transcriptional unit carrying both c abl and bcr genetic information whose transcript is a new fused mRNA of 8 . 5 kilobases ( kb ) and whose translational product is a 210 kD phosphoprotein with tyrosine kinase activity implicated in the pathogenesis of CML . ^^^ In the third patient a chimeric mRNA was detected by a c abl cDNA probe but failed to hybridize with a bcr cDNA probe and showed very low hybridization levels with further 5 ' bcr cDNA probes . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In situ hybridization studies revealed a translocation of the c abl oncogene to the Ph chromosome and Northern blot analysis identified a chimeric 8 kb bcr / abl RNA transcript in leukemic cells . ^^^ These data suggest that 1 . less bcr coding sequences than previously assumed may be essential for the putative transforming activity of the rearranged bcr / abl gene and 2 . the bcr probes currently used for diagnostic purposes could miss Ph positive CML cases . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Rearrangement of bcr and c abl sequences in Ph positive acute leukemias and Ph negative CML an update . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The chronic myelogenous leukemia specific P 210 protein is the product of the bcr / abl hybrid gene . ^^^ Chronic myelogenous leukemia ( CML ) is a human disease associated with a consistent chromosomal translocation that results in sequences from the c abl locus on chromosome 9 being fused to sequences in a breakpoint cluster region ( bcr ) on chromosome 22 . ^^^ CML cells have two novel products : an 8 . 5 kilobase RNA transcript containing both abl and bcr and a 210 kilodalton phosphoprotein ( P 210 ) recognized by 5 abl specific antisera . ^^^ To test whether the P 210 is the product of the novel 8 . 5 kilobase bcr / abl fusion transcript , antibodies were prepared against c abl and bcr determinants . ^^^ By analogy to the gag / abl fusion protein of Abelson murine leukemia virus , the replacement of amino terminal c abl sequences by bcr sequences in P 210 may create a transforming protein involved in CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Persistence of chronic myelocytic leukemia despite deletion of rearranged bcr / c abl sequences in blast crisis . ^^^ Moreover , Southern blot analyses of blastic cells exhibited a rearrangement within bcr , but a deletion of 5 ' bcr sequences , and Northern blots failed to detect the hybrid 8 . 5 kb bcr / c abl transcript usually observed in Ph+ CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In vitro transformation of immature hematopoietic cells by the P 210 BCR / ABL oncogene product of the Philadelphia chromosome . ^^^ RNA splicing joins sequences from a gene on chromosome 22 ( BCR ) across the translocation breakpoint to a portion of the ABL oncogene from chromosome 9 , resulting in a chimeric protein ( P 210 ) that is an active tyrosine kinase . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Alternative splicing occurs at the same site at which bcr sequences join to abl sequences in the Philadelphia chromosome translocation . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Based on our sequence analysis , we propose that initiation of translation occurs at nucleotide 471 , such that the initial 927 amino acids of P210c abl are derived from BCR sequences . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Perhaps one of the most striking examples of this association occurs in chronic myelogenous leukaemia , where the Philadelphia ( Ph ) translocation results in substitution of the 5 ' end of the c abl proto oncogene with bcr gene sequences . ^^^ Here we report that the Ph translocation in acute lymphoblastic leukaemia can result in production of a novel aberrant c abl protein that is distinct from the bcr abl protein found in Ph positive chronic myelogenous leukaemia . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The translocation of the c abl oncogene from chromosome 9 to the bcr gene on chromosome 22 in cases of Philadelphia chromosome positive chronic myelogenous leukemia ( CML ) generates an aberrant bcr abl fusion transcript which may be intimately related to the pathogenesis of CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
C abl and bcr are rearranged in a Ph 1 negative CML patient . ^^^ Using molecular approaches we demonstrate ( 1 ) a rearrangement within the CML breakpoint cluster region ( bcr ) on chromosome 22 , and ( 2 ) a joint translocation of bcr and c abl oncogene sequences to the derivative chromosome 12 . ^^^ These observations support the view that sequences residing on both chromosome 9 ( c abl ) and 22 ( bcr ) are involved in the generation of CML and suggest that a subset of Ph 1 negative patients may in fact belong to the clinical entity of Ph 1 positive CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Evidence of a new chimeric bcr / c abl mRNA in patients with chronic myelocytic leukemia and the Philadelphia chromosome . ^^^ All five had chimeric bcr / c abl messenger RNA , suggesting that the deleterious effects of this disease can be associated with an abnormal chimeric protein encoded by the bcr and the c abl oncogene . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
By in situ hybridization studies , however , we demonstrate a reciprocal translocation of sequences from chromosome 9 ( c abl ) to Ph 1 and chromosome 22 ( bcr ) to 9 , respectively . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The study of these events led to the identification of the key genes involved ( BCR , ABL , C MYC , RB 1 and N MYC ) and served as models for substantial further work . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Introduction of the BCR / ABL oncogene into this cell line resulted in factor independent proliferation and constitutive phosphorylation of p95Vav . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
At the molecular level the c abl gene from chr . 9 is translocated to the bcr gene on chr . 22 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Leukemic cells from two patients with Philadelphia negative chronic myeloid leukemia ( CML ) were investigated : 1 ) Cytogenetics showed a normal 46 , XY karyotype in both cases , 2 ) molecular studies revealed rearrangement of the M BCR region and formation of BCR ABL fusion mRNA with b2a2 ( patient 1 ) or b3a2 ( patient 2 ) configuration , and 3 ) fluorescence in situ hybridization ( FISH ) demonstrated relocation of the 5 ' BCR sequences from one chromosome 22 to one chromosome 9 . ^^^ The ABL probe hybridized to both chromosomes 9 at band q 34 , while two other probes which map centromeric and telomeric of BCR on 22q11 hybridized solely with chromosome 22 . ^^^ For the first time , a BCR ABL rearrangement is shown to take place on 9q34 instead of in the usual location on 22q11 . ^^^ The few aberrant chromosomal localizations of BCR ABL recombinant genes found previously were apparently the result of complex and successive changes . ^^^ Furthermore in patient 2 , both chromosomes 9 showed positive FISH signals with both ABL and BCR probes . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The Ph chromosome is a translocation chromosome which gains oncogenic potential through the fusion of the ABL oncogene of chromosome 9 with the BCR gene of chromosome 22 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The 145 kDa protein , which appears , from antiphosphotyrosine blots of two dimensional O ' Farrell gels , to exist in four different phosphorylation states following cytokine stimulation ( with isoelectric points ranging from 7 . 2 to 7 . 8 ) , does not appear to be immunologically related to the beta subunit of the interleukin 3 receptor , c Kit , BCR , ABL , JAK 1 , JAK 2 , Sos 1 , eps 15 , or insulin receptor substrate 1 protein . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BCR / ABL fusion located on chromosome 9 in chronic myeloid leukemia with a masked Ph chromosome . ^^^ Furthermore , cohybridization with two differently labeled BCR / ABL translocation DNA probes indicated a BCR / ABL fusion apparently located on 9q34 . ^^^ Molecular studies revealed a rearrangement of the BCR region and expression of a chimeric BCR / ABL mRNA of CML configuration . ^^^ These findings indicate that the BCR / ABL fusion resulted from an unusual relocation of the BCR gene from its normal position on 22q11 to 9q34 adjacent to the ABL gene . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
However , rearrangements of both BCR and ABL genes were detected . ^^^ Comigration between the rearranged fragments obtained with M bcr 5 ' and ABL exon 1B probes was observed , implying that the entire ABL gene was fused to the 5 ' part of the BCR gene . ^^^ Fluorescence in situ hybridization ( FISH ) analyses using BCR and ABL probes showed that in 20 % of metaphases BCR and ABL signals were present on one chromosome 6 at 6p23 , whilst in 80 % of metaphases BCR and ABL signals were identified on both copies of chromosome 6 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Reversed BCR / ABL rearrangement detected by FISH in Philadelphia negative chronic myelocytic leukemia . ^^^ Molecular studies revealed rearrangement of the M bcr region and formation of BCR / ABL fusion mRNA with b3a2 configuration . ^^^ Fluorescence in situ hybridization ( FISH ) using the abl probe showed signal on both chromosomes 9 band q 34 , while the bcr probe hybridized to one chromosome 22 and to one chromosome 9 . ^^^ In this case , as in three other cases recently described ( Hagemeijer et al . and Nachava et al . ) , the bcr / abl rearrangement is shown to be on 9q34 , instead of the usual location on 22q11 . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In chronic myeloid leukemia ( CML ) the proto oncogene c abl from chromosome 9 q 34 is translocated to the breakpoint cluster region ( bcr ) gene on chromosome 22 q 11 . ^^^ This translocation results in a BCR ABL fusion gene , which encodes chimeric fusion oncoproteins p210BCR ABL . ^^^ Here we demonstrate that a peptide with joining region sequence ATGFKQSSKALQRPVAS ( eight amino acids ( aa ) encoded by BCR exon 3 ; one novel lysine , encoded by the fusion codon ; eight aa encoded by ABL exon 2 ) is immunogenic to human T cells . ^^^ Primary immune response induction with this peptide resulted in a HLA DR 2 ( DRB1 * 1501 ) restricted CD4+ BCR ABL peptide specific T cell line P 1 . ^^^ Since presentation of cytosolic oncoproteins as peptides by DR molecules has been observed , the present findings provide a possible explanation for post interferon alpha persisting remissions in spite of the presence of BCR ABL PCR positive progenitors . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
This gene has been mapped to the chromosome 9q33 34 . 1 , the same region as the reciprocal translocation that creates the breakpoint cluster region ( BCR ) ABL chimera of the Philadelphia chromosome ( Ph ' ) . ^^^ To investigate the possible involvement between the BCR ABL fusion gene and hLH 2 in the pathogenesis of CML , an hLH 2 negative CML cell line , JK 1 that carries double Ph ' chromosomes , was examined . ^^^ Like other CML cells , high BCR ABL fusion mRNA levels are expressed , but no transcript of hLH 2 was detected in JK 1 cells as determined by reverse transcriptase polymerase chain reaction ( RT PCR ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Establishment and molecular characterization of a novel leukemic cell line with Philadelphia chromosome expressing p 230 BCR / ABL fusion protein . ^^^ The cell line AR 230 was established from the peripheral blood mononuclear cells of a patient with chronic myeloid leukemia and t ( 9 ; 22 ) translocation bearing a variant type of BCR / ABL rearrangement . ^^^ AR 230 expresses a BCR / ABL fusion protein with a molecular mass of 230 kilodaltons ( kDa ) due to the insertion of 180 amino acids encoded by 3 ' exons of BCR ( b 4 to c 3 ) . ^^^ An immune complex kinase assay showed that the 230 kDa BCR / ABL protein ahd autophosphorylation activity . ^^^ Immunoprecipitation analysis revealed a stable complex of GRB 2 and 230 kDa BCR / ABL proteins , indicating that the Ras activation pathway is involved in the process of transformation . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Reply to Haas : Are ABL and BCR imprinted . ( Leukemia 1995 ; 9 : 740 743 ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Sequence and analysis of the human ABL gene , the BCR gene , and regions involved in the Philadelphia chromosomal translocation . ^^^ The complete human BCR gene ( 152 141 nt ) on chromosome 22 and greater than 80 % of the human ABL gene ( 179 512 nt ) on chromosome 9 have been sequenced from mapped cosmid and plasmid clones via a shotgun strategy . ^^^ Because these two chromosomes are translocated with breakpoints within the BCR and ABL genes in Philadelphia chromosome positive leukemias , knowledge of these sequences also might provide insight into the validity of various theories of chromosomal rearrangements . ^^^ Comparison of these genes with their cDNA sequences reveal the positions of 23 BCR exons and putative alternative BCR first and second exons , as well as the common ABL exons 2 11 , respectively . ^^^ Additionally , these regions include the alternative ABL first exons 1b and 1a , a new gene 5 ' to the first ABL exon , and an open reading frame with homology to an EST within the BCR fourth intron . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Division of the samples into those patients who had lost exon b 3 during the formation of the BCR / ABL gene and those that had retained exon b 3 produced differing patterns of methylation during disease progression . ^^^ The former group , who also expressed a b 2 a2 mRNA , showed an increase in methylation of the non rearranged BCR gene prior to and during blast crisis , with a inverse decrease in the methylation of the BCR / ABL gene . ^^^ Those patients who had retained exon b 3 , and expressed a b 3 a2 mRNA , showed no change in the extent of methylation of the BCR / ABL gene but did exhibit an increase in methylation of the BCR gene during blast crisis . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Detection of bcr abl fusion mRNA in chronic myelogenous leukemia by reverse transcription polymerase chain reaction using nested primers . ^^^ Chronic myelogenous leukemia ( CML ) is identified by an unique t ( 9 ; 22 ) translocation which fuses the abl gene to the breakpoint cluster region ( bcr ) gene . ^^^ We constructed a sensitive and specific system for detection of CML specific mRNA even in minute amounts of leukemic cells that expressed bcr abl fusion mRNA in CML patient blood . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Detection of M bcr / abl fusion by fluorescence in situ hybridization ( FISH ) in a case of Ph negative CML . ^^^ Thus , molecular rearrangement of bcr resulted from insertion of an abl gene within the bcr region despite absence of a Ph chromosome . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Late appearance of a Philadelphia translocation with minor BCR / ABL transcript in a t ( 7 ; 11 ) ( p 15 ; p 15 ) acute myeloid leukemia . ^^^ A BCR / ABL transcript was detected at the second relapse by reverse transcription polymerase chain reaction assay ; the leukemic cells had a BCR / ABL fusion gene involving the minor breakpoint cluster region ( minor BCR ; situated in intron 1 of the BCR gene ) . ^^^ Moreover , minor BCR / ABL rearrangements may also occur as a late appearance of Ph translocation . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Balanced parental contribution to the ABL component of the BCR ABL gene in chronic myeloid leukemia . ^^^ This parental bias led to the hypothesis that the genes disrupted by the translocation , BCR and ABL , were themselves imprinted , and that in CML the BCR ABL gene was formed by BCR sequences of maternal and ABL sequences of paternal origin . ^^^ Amplification of the specific BCR ABL and normal ABL mRNA messages by reverse transcriptase polymerase chain reaction in these patients showed that the ABL moiety of the BCR ABL gene has an even chance of being the paternal or the maternal copy . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Are ABL and BCR imprinted . ^^^ The apparent nonrandom contribution of the paternally derived chromosome 9 and the maternally derived chromosome 22 to the leukemia specific translocation t ( 9 ; 22 ) ( q 34 ; q 11 ) obtained by cytogenetic analysis suggested that the two genes affected by this rearrangement , namely ABL and BCR , are imprinted . ^^^ The results of recent molecular genetic studies have challenged this notion , since it was shown that both the paternal as well as the maternal BCR and ABL alleles may be affected by the translocation event and that both genes may be expressed from both alleles . ^^^ Based on the few available data concerning their allelic methylation pattern , replication behavior and expression status , as well as by referring to similar problems encountered in other genes whose imprinting status had also remained elusive for a long time , 1 argue that it still remains likely that ABL and BCR are imprinted . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Multi unit ribozyme mediated cleavage of bcr abl mRNA in myeloid leukemias . ^^^ Chronic myelogenous leukemia is characterized by the Philadelphia chromosome , which at the molecular level results from the fusion of the bcr gene on chromosome 22 and the abl gene on chromosome 9 . ^^^ The bcr abl fusion gene encodes a novel tyrosine kinase with transforming activity . ^^^ In this study , we have synthesized a multi unti ribozyme that targets bcr abl mRNA . ^^^ The multiunit ribozyme was then transfected into murine myeloblasts transformed with the bcr abl gene ( 32D cells ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Standpoint on imprinting of BCR and ABL . ^^^ These data have suggested that the two genes BCR and ABL , which become fused through the translocation , might be imprinted , ie expressed in a parental specific manner . ^^^ Recent molecular genetic studies however , have shown that BCR and ABL are expressed on both alleles and that the maternal and paternal ABL genes contribute equally often to the BCR ABL fusion messenger . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The disruption of the BCR gene and its juxtaposition to and consequent activation of the ABL gene has been implicated as the critical molecular defect in Philadelphia chromosome positive leukemias . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Interferon response in chronic myeloid leukaemia correlates with ABL / BCR expression : a preliminary study . alpha Interferon ( IFN ) has been used to induce cytogenetic remission in chronic myeloid leukaemia ( CML ) , but there are few indicators to predict IFN response . ^^^ The role of the chimaeric BCR / ABL gene in the malignant process is undisputed . ^^^ The function and clinical significance of the newly discovered ABL / BCR mRNA has not been investigated for a correlation with CML prognosis or response to therapy . ^^^ We have used a two step reverse transcriptase polymerase chain reaction ( RT PCR ) to detect the transcripts of the chimaeric genes BCR / ABL , ABL / BCR , as well as the normal ABL and BCR genes in 24 CML patients treated with IFN . ^^^ Also , no correlation was found between expression of BCR , ABL or BCR / ABL mRNA and response to treatment with IFN . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The theory is based on the assumption that incorrect or unfaithful rejoining of initial double strand breaks produced concurrently within the 200 kbp intron region upstream of the second abl exon , and the 16 . 5 kbp region between bcr exon 2 and exon 6 interact with each other , resulting in a fusion gene . for an 10 ray dose of 100 Gy , there is good agreement between the theoretical estimate and the one available experimental result . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
By transcription and translation of the ABL oncogene attached to gene BCR and belonging to the 22nd chromosome a fusion protein with a high kinase activity is formed which is typical for the pathological clone of haematopoietic cells in chronic leukaemia . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BCR ABL is a chimeric oncogene generated by translocation of sequences from the c abl protein tyrosine kinase gene on chromosome 9 into the BCR gene on chromosome 22 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Characterization of genomic BCR ABL breakpoints in chronic myeloid leukaemia by PCR . ^^^ In order to understand better the mechanism of translocation between the BCR and ABL genes in CML , we have exploited a ' bubble PCR ' technique to clone genomic breakpoints . ^^^ BCR ABL junction fragments were successfully amplified and sequenced in 14 / 32 ( 43 % ) patients tested . ^^^ In three cases Alu sequences were found at or near the breakpoint on the ABL side of the translocation but no other obvious sequence homologies were found either in BCR or ABL . ^^^ The translocation event was characterized further in three other patients by amplifying the reciprocal ABL BCR junction on the 9q+ chromosome and also normal ABL around breakpoints . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In human leukemia , activation of the ABL proto oncogene locus on chromosome 9 most commonly occurs as a result of its fusion to the BCR locus on chromosome 22 . ^^^ Like BCR , TEL is fused in frame with ABL and produces a fusion protein with an elevated tyrosine kinase activity when assayed in an immune complex . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
CML patients possess either a b 3 a2 or a b 2 a2 fusion between the BCR and ABL genes . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
More than 95 % of the patients with chronic myelogenous leukemia ( CML ) carry translocations between protooncogene abl of chromosome 9 and bcr gene of chromosome 22 , resulting in the Philadelphia chromosome ( Ph 1 ) . ^^^ In the detection phase two oligonucleotide probes were used in the hybridization reaction , one biotinylated ( bcr gene , exon 2 ) and one ( abl gene ) labeled with Eu3+ . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The SH 2 domain of ABL is not required for factor independent growth induced by BCR ABL in a murine myeloid cell line . ^^^ Chronic myelogenous leukemia ( CML ) is characterized by the presence of a specific chromosomal translocation between the long arms of chromosomes 9 and 22 that results in the fusion of BCR encoded sequences upstream of exon 2 of c ABL . ^^^ This fusion gene produces a 210 kDa chimeric BCR ABL protein that has elevated tyrosine kinase activity . ^^^ However , their necessity for the transforming functions of BCR ABL has not been determined . ^^^ A specific deletion of the SH 2 domain of ABL was created to determine whether this mutation would alter the ability of BCR ABL to induce factor independent growth of a murine myeloid cell line and to determine whether the SH 2 domain mediates the interaction of BCR ABL with any of its substates . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Philadelphia ( Ph ) positive leukemias invariably contain a chromosomal translocation fusing BCR to ABL . ^^^ The BCR ABL protein is responsible for leukemogenesis . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Heterogeneity of the breakpoint in the ABL gene in cases with BCR / ABL transcript lacking ABL exon a 2 . ^^^ We report cases with a variant BCR / ABL mRNA expression lacking ABL exon a 2 sequences . ^^^ Two of these cases showed major breakpoint cluster region ( BCR ) exon 3 ( b 3 ) and ABL exon 3 ( a 3 ) junction ( b3 / a3 ) , while the other case showed minor BCR exon 1 ( e 1 ) and a 3 junction ( e1 / a3 ) . ^^^ Two of these cases , however , were found to have a breakpoint in the ABL gene outside of the intron between exons a 2 and a 3 , probably 5 ' upstream of exon a 2 , suggesting that the BCR exon was spliced to ABL exon a 3 . ^^^ These findings differ from those previously reported , in which the breakpoints in the ABL gene were between exons a 2 and a 3 , and indicate a novel mechanism for the deletion of ABL exon a 2 sequences in the formation of a variant BCR / ABL fusion transcript . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
A novel variant of the bcr abl fusion product in Philadelphia chromosome positive acute lymphoblastic leukemia . ^^^ Two patients with Philadelphia chromosome positive acute lymphoblastic leukemia showed novel variants of the chimeric bcr abl mRNA . ^^^ The bcr abl breakpoint region on cDNA derived from the chimeric mRNA was amplified using the polymerase chain reaction ( PCR ) . ^^^ Sequence analysis of the breakpoint containing fragment showed that in both patients exon a 2 of the abl gene was deleted , giving rise to an in frame joining at the mRNA level of 5 ' bcr sequences to the abl exon a 3 . ^^^ Protein studies showed a bcr abl protein with heightened tyrosine kinase activity in blast cells of both patients : one of the P 190 type , the other of the P 210 type . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The bcr abl fusion gene situated on the Philadelphia chromosome is a tumor specific marker for chronic myelogenous leukemia . ^^^ We evaluated the usefulness of two color fluorescence in situ hybridization with bcr and abl probes as a means of detecting the Philadelphia chromosome in formalin fixed , paraffin embedded sections of spleen and lymph node specimens from eight patients with myeloproliferative diseases showing clinical and morphological features of chronic myelogenous leukemia in accelerated phase . ^^^ Our analysis showed co localized hybridization signals corresponding to the bcr abl fusion product in tissue sections from six patients previously found to have the Philadelphia chromosome by conventional cytogenetics and polymerase chain reaction . ^^^ The two remaining specimens lacked bcr abl fusion signals and were obtained from patients who were negative for the Philadelphia chromosome by cytogenetic and polymerase chain reaction analysis . ^^^ We conclude that fluorescence in situ hybridization is a sensitive method for the detection of the bcr abl fusion gene in histological specimens from patients with chronic myelogenous leukemia . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Progressive de novo DNA methylation at the bcr abl locus in the course of chronic myelogenous leukemia . ^^^ After the t ( 9 ; 22 ) chromosomal translocation and generation of the Philadelphia chromosome , the initiating event in chronic myelogenous leukemia ( CML ) , most of the abl coding sequence is fused to the 5 ' region of the bcr gene . ^^^ Expression of the hybrid bcr abl gene is , therefore , regulated by the bcr promoter . ^^^ In most cases of CML , one of the two abl promoters ( Pa ) is nested within the bcr abl transcriptional unit and should be able to transcribe the type Ia 6 kb normal abl mRNA from the Philadelphia chromosome . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Philadelphia negative chronic myeloid leukaemia : detection by FISH of BCR ABL fusion gene localized either to chromosome 9 or chromosome 22 . ^^^ Co localization of signals from BCR and ABL cosmids was observed in interphase nuclei from both patients . ^^^ In a second patient 5 ' BCR sequences were missing from one copy of chromosome 22 , and co localized with 3 ' ABL sequences on chromosome 9 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic myeloid leukemia presenting ALL type BCR / ABL transcript . ^^^ By Southern blot , the breakpoint was not identified on M bcr in three CML cases , of which one case showed the P 210 type bcr / abl transcript and two cases showed the ALL type ( P 190 type ) bcr / abl transcript with or without P 210 transcript . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
ABL and BCR genes are not imprinted in androgenetic and gynogenetic human tissues . ^^^ In the translocation leading to the formation of the Philadelphia chromosome , the hallmark of chronic myeloid leukemia ( CML ) , the translocated chromosome 9 ( ABL ) , is of paternal descent whereas chromosome 22 ( BCR ) is of maternal origin ( 1 ) . ^^^ To study possible imprinting of the human ABL and BCR genes , we used human tissues exclusively endowed with their maternally ( benign teratoma ) or paternally ( complete hydatidiform mole ) inherited chromosomes . ^^^ Using the sensitive PCR technique followed by northern blotting , we demonstrate here that ABL and BCR are expressed to a similar extent in androgenetic and gynogenetic human tissues , thus suggesting that ABL and BCR genes are not imprinted in these human tissues . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
This acquired karyotypic abnormality is the product of a balanced translocation between the c abl oncogene on chromosome 9 and the breakpoint cluster region ( BCR ) gene on chromosome 22 . ^^^ The resulting BCR / c abl hybrid gene is actively transcribed and is considered essential in the pathogenesis of this disease . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Therefore , to clarify this possibility , an examination was made to see whether genetic changes such as BCR ABL translocation closely associated with chronic myelogenous leukemia ( CML ) are actually induced by radiation . ^^^ BCR ABL translocation is easily detected by means of reverse transcription polymerase chain reaction . ^^^ One hundred million cells of the promyelocytic leukemia derived cell line HL 60 , which do not have such a gene rearrangement , were irradiated with 100 Gy of 10 ray , after which RNA was extracted and examined for any rearrangements of BCR and ABL genes . ^^^ Five kinds of bands were observed in the HL 60 cells irradiated with 100 Gy of 10 ray , and it became clear that these positive bands contain both BCR gene and ABL gene by the direct sequencing method . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
T lymphocytes in chronic myelogenous leukaemia ( CML ) : no evidence of the BCR / ABL fusion gene detected by fluorescence in situ hybridization in 14 patients . ^^^ To examine the possibility that the occasional CML patient might have major penetration of the T cell compartment by the leukaemic clone , we studied interphase T cells from the blood of 11 CML patients conventionally treated in chronic phase and three in relapse after allogeneic bone marrow transplant ( BMT ) by fluorescence in situ hybridization using BCR and ABL cosmid probes . ^^^ Cells with juxtaposition of BCR and ABL signals or with the two signals up to one signal diameter apart were scored as positive . ^^^ We conclude that none of the patients studied by this technique had any appreciable proportion of BCR / ABL positive T cells in the circulation . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Neither Ph chromosome , nor cabl and bcr gen rearrangement were demonstrated , but the expression and amplification of c myc oncogene indicated disease progression . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BCR and ABL gene fragments were used as probes for the detection of the BCR / ABL fusion product in peripheral blood and bone marrow cells from 11 CML patients in which 5 were post BMT . ^^^ FISH demonstrated a high degree of sensitivity ( 1 % ) for the detection of the BCR / ABL translocation in these patients . ^^^ A linear correlation was found between FISH detection of the BCR / ABL fusion product and routine chromosomal analysis ( r = 0 . 995 ; p < 0 . 001 ) . ^^^ Detection of the BCR / ABL signal by FISH was observed in all patients showing a positive PCR signal . ^^^ A significant reduction in BCR / ABL signal was observed post transplant ( p < 0 . 001 ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
To make differential diagnosis , leukemia blasts at onset and relapse were examined for rearrangement of immunoglobulin JH gene and bcr / abl fusion mRNA , and were found to have the same JH gene rearrangement pattern and the same bcr / abl mRNA of bcr exon 2 / abl exon 2 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In chronic myelogenous leukemia the human c abl protooncogene from chromosome 9 is translocated to the specific breakpoint cluster ( bcr ) region on chromosome 22 . ^^^ The joining region segment of chimeric bcr abl protein is composed of a unique combination of c abl and bcr amino acids and is expressed only by malignant cells . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BCR ABL maintains resistance of chronic myelogenous leukemia cells to apoptotic cell death . ^^^ Here we show that K 562 , a chronic myelogenous leukemia ( CML ) cell line expressing the BCR ABL fusion protein , are resistant to the induction of apoptosis by a number of agents and conditions . ^^^ Antisense oligodeoxynucleotides corresponding to the translation start of bcr downregulate bcr abl protein in these cells and render them susceptible to induction of apoptosis by chemotherapeutic agents or serum deprivation . ^^^ These data indicate that bcr abl acts as an anti apoptosis gene in CML cells and suggests that the effect is dependent on the abl kinase activity in this chimeric protein . ^^^ Inhibition of bcr abl to render CML cells susceptible to apoptosis can be combined with therapeutic drugs and / or treatment capable of inducing apoptosis to provide an effective strategy for elimination of these cells . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Molecular consequences of the BCR ABL translocation in chronic myelogenous leukemia . ^^^ The BCR ABL translocation of chronic myelogenous leukemia represents a paradigm for the study of translocations that create fusion proteins . ^^^ The work of many laboratories has clearly established that the BCR ABL protein can transform cells and cause leukemias in mice . ^^^ Although the biological effects of the BCR ABL fusion protein are well characterized , the normal biological functions of ABL and BCR are only beginning to come to light . ^^^ Understanding the normal roles of ABL and BCR will help define the abnormal leukemogenic effects of the BCR ABL fusion . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Several components of p210bcr / abl are thought to be essential for its transforming activity : These include the constitutive tyrosine kinase activity of abl and the ability of the first exon for bcr both to specifically bind to abl ' s SH 2 binding domain and possibly also to function as a novel type of serine kinase . ^^^ Relatively little is yet known about what specific abnormalities in the regulatory pathways are caused by the altered tyrosine kinase activity of p210bcr / abl and other bcr / abl oncoproteins , but whatever its precise mode of action proves to be , p210bcr / abl presumably somehow changes the normal pattern of phosphorylation of key regulatory proteins in the signaling pathways so that the genes which normally direct the orderly sequence of proliferation and maturation of the myeloid progenitors are not properly regulated . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Lack of reciprocal translocation in BCR ABL positive Ph negative chronic myeloid leukaemia . ^^^ We used fluorescence in situ hybridization ( FISH ) to metaphase chromosomes with BCR and ABL cosmid probes in conjunction with the polymerase chain reaction ( PCR ) to study the mechanism by which the ABL proto oncogene is inserted into a morphologically normal chromosome 22 in patients with Ph negative chronic myeloid leukaemia characterized by the BCR ABL chimeric gene . ^^^ In control patients with Ph positive CML the ABL probe localized to 22q and the 3 ' BCR probe localized to 9q+ . ^^^ By PCR all had evidence of BCR ABL transcripts , but none had evidence of the reciprocal ABL BCR gene product that is seen in 70 % of the Ph positive CML patients . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Selective cleavage of bcr abl chimeric RNAs by a ribozyme targeted to non contiguous sequences . ^^^ Novel approaches for ribozyme targeting were developed by using the L 6 bcr abl fusion RNA as a model . ^^^ Using one approach , we successfully directed ribozyme nucleation to a site on the bcr abl RNA that is distant from the GUA cleavage site . ^^^ Ribozymes generated by a second approach were designed to cleave at a CUU site in proximity to the bcr abl junction . ^^^ Both approaches have led to the development of a series of ribozymes specific for both the L 6 and K 28 bcr abl chimeric RNAs , but not normal abl or bcr RNAs . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
A different mechanism of oncogene activation in a leukaemia specific chromosomal abnormality is found for CML , where c abl sequences are fused into the bcr locus , or in the t ( 4 ; 11 ) of acute childhood leukaemia involving the recently identified ALL 1 gene at chromosome 11q23 resulting in a malfunctioning , structurally altered oncogene . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
This translocation results in the fusion of the ABL and the BCR genes to form a BCR / ABL fusion gene , the product of which has a greatly increased protein tyrosine kinase activity in comparison with the normal ABL protein . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chromosomal and molecular analyses , including BCR rearrangement and BCR ABL mRNA , before and after IFN alpha treatment demonstrated a recovery of normal hematopoiesis by the treatment of INF alpha , however , suppressive effect for the blast cells by IFN alpha was insufficient . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The procedure allows detection of as few as 1 % Ph+ cells independent of the cycling status or BCR / ABL expression level of cells , and the quantitation of non Ph chromosome containing interphase nuclei in the marrow of patients judged 100 % Ph+ by standard cytogenetics . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic myelogenous leukemia is characterized by a specific chromosomal translocation , t ( 9 ; 22 ) , in which the ABL protooncogene and the BCR gene become juxtaposed . ^^^ The chimeric BCR / ABL gene produces a P 210 fusion protein with deregulated tyrosine kinase activity . ^^^ In the current study , we show that CRKL is highly phosphorylated in the chronic myelogenous leukemia cell line K 562 and that it is a substrate for the p 210 BCR / ABL and p 145 ABL kinases . ^^^ BCR / ABL and ABL are coimmunoprecipitated with CRKL in vivo , demonstrating that relatively stable complexes are formed . ^^^ These findings establish a putative signal transduction pathway way through which BCR / ABL mediates its oncogenic activity . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic myeloid leukemia ( CML ) is a clonal disorder arising from the hematopoietic stem cell , characterized by the Philadelphia chromosome ( Ph ) and , at the molecular level , by fusion of the BCR ( breakpoint cluster region ) gene and the c ABL gene . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Author ' s reply to `` Rearrangement of the BCR / ABL and TCR beta genes in lymph node blast crisis diagnosed of chronic myeloid leukemia ' ' . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In vitro and in vivo effects of synthetic ribozymes targeted against BCR / ABL mRNA . ^^^ Chronic myelogenous leukemia ( CML ) is associated with a translocation of the BCR and the ABL genes , t ( 9 ; 22 ) . ^^^ We therefore designed synthetic ribozymes which are capable of exclusively cleaving the BCR / ABL B3A2 type mRNA without altering normal cellular transcripts . ^^^ Quantitative PCR analyses showed an up to fivefold reduction of the relative number of BCR / ABL mRNA molecules per single cell after exposure to ribozymes compared to controls . ^^^ We conclude that ribozymes targeted against the B3A2 type BCR / ABL mRNA function in vitro and in vivo . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BCR and ABL gene rearrangement in chronic myeloid leukemia ] . ^^^ The fact of chromosome 9 and 22 translocation connected with the fusion of BCR and ABL genes occurring in 95 % patients with chronic myeloid leukemia ( CML ) enables us to use molecular biology methods in CML diagnosis . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Analysis of BCR / ABL abnormalities in mRNA from 20 year old paraffin embedded tissue for BCR / ABL rearrangement by polymerase chain reaction . ^^^ Spleen tissue from 6 subjects with chronic myelogenous leukemia was studied for rearrangement of BCR and ABL genes . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Ribozyme mediated cleavage of the bcr / abl transcript expressed in chronic myeloid leukemia . ^^^ The bcr / abl transcript is specifically expressed in the hematopoietic cells of patients with chronic myeloid leukemia ( CML ) . ^^^ Cleavage of the normal bcr was also noted but at a reduced efficiency compared to that exhibited for the bcr / abl substrate . ^^^ Importantly , cleavage of the full length bcr / abl mRNA was achieved at physiologic temperature , demonstrating effective ribozyme mediated cleavage . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
A coiled coil oligomerization domain of Bcr is essential for the transforming function of Bcr Abl oncoproteins . ^^^ In Philadelphia chromosome positive human leukemias , the c abl proto oncogene on chromosome 9 becomes fused to the bcr gene on chromosome 22 , and chimeric Bcr Abl proteins are produced . ^^^ The fused Bcr sequences activate the tyrosine kinase , actin binding , and transforming functions of Abl . ^^^ Activation of the Abl transforming function has been shown to require two distinct domains of Bcr : domain 1 ( Bcr amino acids 1 to 63 ) and domain 2 ( Bcr amino acids 176 to 242 ) . ^^^ Tetramerization of Bcr Abl through Bcr domain 1 correlates with activation of the tyrosine kinase and F actin binding functions of Abl . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
However , CML without rearrangements of ABL and BCR genes , called `` atypical CML ' ' , forms a separate entity showing clinical and morphological features different from classical CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Disease progression in a murine model of bcr / abl leukemogenesis . ^^^ We have developed a system for expressing bcr / abl genes in the mouse hematopoietic system utilizing retroviral gene transfer and bone marrow transplantation . ^^^ Studies of this system and related systems in other laboratories have begun to yield insights into the pathophysiology of the human bcr / abl leukemias . ^^^ The P 190 form of bcr / abl appears to be more potent in leukemogenesis than P 210 , but may also be associated with a CML like picture upon infection of a multipotential target cell . ^^^ There may be a spectrum of different chronic phase duration associated with different Bcr / Abl proteins , with bcr sequences influencing the rate of disease progression . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The role of myc in transformation by BCR ABL . ^^^ The BCR ABL gene plays a central role in the pathogenesis of chronic myelogenous leukemia . ^^^ Despite a detailed understanding of the regions of BCR and ABL required for transformation by BCR ABL , little is known about the signalling pathway by which BCR ABL causes transformation . ^^^ The nuclear oncogene c myc plays a critical role in BCR ABL transformation . ^^^ Levels of c myc RNA are high in cells transformed by BCR ABL , and overexpression of dominant negative forms of myc blocks transformation by BCR ABL . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Structural organization of BCR ABL gene in chronic phase and blast transformation in chronic myeloid leukemia patients . ^^^ The activation of BCR ABL involves direct interaction between BCR first exon sequences and the tyrosine kinase regulatory domains of ABL . ^^^ These domains are essential for BCR ABL mediated transformation . ^^^ Our results demonstrate the presence of point mutation in this regulatory region , which may suggest a role for the altered BCR sequence in activation of the BCR ABL oncogene . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Detection of the BCR / ABL fusion gene in chronic myeloid leukemia by RNA polymerase chain reaction . ^^^ The bcr / abl fusion gene in 20 patients with chronic myeloid leukemia ( CML ) was detected by RNA polymerase chain reaction , which used mRNA as the starting material to generate cDNA with reverse transcriptase followed by PCR amplification ( RNA / PCR ) . ^^^ Amplification of a sequence spanning the bcr / abl junction region was achieved by using peripheral blood cells as the source of mRNA from all 20 patients with CML , including 3 cases of Ph ( ) CML , and cell line K 562 was derived from patients with CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The Philadelphia chromosome , detected in virtually all cases of chronic myelogenous leukemia , is formed by a reciprocal translocation between chromosomes 9 and 22 that fuses BCR encoded sequences upstream of exon 2 of c ABL . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Deletion of chromosome 22 without bcr rearrangement and without juxtaposition of c abl in a case of acute myeloid leukemia . ^^^ Southern blot analysis showed no bcr rearrangement and fluorescence in situ hybridization indicated no juxtaposition of c abl . ^^^ This study indicates that molecular events other than bcr rearrangement and c abl juxtaposition were involved in leukemogenesis in this patient . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The cells exhibited multiple copies of the Philadelphia chromosome , and a high level of p210Bcr Abl kinase activity was detected with rabbit anti Abl and anti Bcr ( exon 3 ) peptide antisera . ^^^ While a normal BCR message was detected , no normal ABL message was found . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Tyrosine phosphorylation of P 160 BCR by P 210 BCR ABL . ^^^ It is well established that the chimeric BCR ABL gene formed by joining parts of the BCR and ABL genes plays a key role in the pathogenesis of Philadelphia ( Ph ) chromosome positive leukemias . ^^^ We report that simultaneous expression of P 210 BCR ABL and P 160 BCR in simian COS 1 cells yielded stable complexes of these two proteins , and induced phosphorylation of P 160 BCR on tyrosine residues in vivo . ^^^ Tyrosine phosphorylation of a deletion mutant encoding 553 amino acids of BCR N terminal sequences was also detected when it was coexpressed with P 210 BCR ABL . ^^^ We propose that tyrosine phosphorylation of P 160 BCR by P 210 BCR ABL and their stable physical interaction may perturb normal BCR functions and that these alterations are directly involved in the pathologic processes found in Ph chromosome associated leukemias . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Reverse transcriptase polymerase chain reaction technique demonstrated the presence of major bcr / abl mRNA . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Both the suppression and the hematological remission have been sustained for 24 months with alpha interferon , in spite of the detection of the chimeric BCR / ABL mRNA in her bone marrow by polymerase chain reaction assay 12 months after therapy . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Usefulness of the rearrangement of the bcr / abl gene in extramedullary ( lymph nodes ) blast crisis diagnosed in chronic myeloid leukaemia . ^^^ The introduction of molecular biological techniques in the study of chronic myeloid leukaemia ( CML ) allows us to show the bcr / abl gene rearrangement produced by the translocation between the c abl proto oncogene located in chromosome 9 and the bcr region located in chromosome 22 , which constitutes the molecular alteration of Philadelphia chromosome in CML . ^^^ We present the usefulness of the bcr / abl gene rearrangement study in the diagnosis of a blast crisis initially located in lymph nodes of a patient with CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
After 4 weeks of LTC , the J ( bcr b3 / ABL 2 ) RNA transcript persisted in the untreated BM , whereas neither BCR / ABL RNA transcripts were detected in the culture established with IFN gamma treated CML BM . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Subcellular localization of Bcr , Abl , and Bcr Abl proteins in normal and leukemic cells and correlation of expression with myeloid differentiation . ^^^ We used specific antisera and immunohistochemical methods to investigate the subcellular localization and expression of Bcr , Abl , and Bcr Abl proteins in leukemic cell lines and in fresh human leukemic and normal samples at various stages of myeloid differentiation . ^^^ In contrast , normal endogenous Bcr protein , as well as the aberrant p210BCR ABL and p190BCR ABL proteins consistently localize to the cytoplasm in both cell lines and fresh cells . ^^^ Because the p210BCR ABL protein appears cytoplasmic in both chronic phase and blast crisis CML cells , as does the p190BCR ABL in Ph 1 positive acute leukemia , a change in subcellular location of Bcr Abl proteins between cytoplasm and nucleus can not explain the different spectrum of leukemias associated with p 210 and p 190 , nor the transition from the chronic to the acute leukemia phenotype seen in CML . ^^^ Further analysis of fresh CML and normal hematopoietic bone marrow cells reveals that p210BCR ABL , as well as the normal Bcr and Abl proteins , are expressed primarily in the early stages of myeloid maturation , and that levels of expression are reduced significantly as the cells mature to polymorphonuclear leukocytes . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
SH 1 domain autophosphorylation of P 210 BCR / ABL is required for transformation but not growth factor independence . ^^^ P 210 BCR / ABL is a chimeric oncogene implicated in the pathogenesis of chronic myelogenous leukemia . ^^^ BCR sequences have been shown to be required for activation of the tyrosine kinase and transforming functions of BCR / ABL . ^^^ In this work , we show that two other structural requirements for full transforming activity of P 210 BCR / ABL include a functional tyrosine kinase and the presence of tyrosine 1294 , a site of autophosphorylation within the tyrosine kinase domain . ^^^ Replacement of tyrosine 1294 with phenylalanine ( 1294F ) greatly diminishes the transforming activity of BCR / ABL without affecting the specific activity of the protein tyrosine kinase . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The ABL BCR fusion gene is expressed in chronic myeloid leukemia . ^^^ Although the BCR ABL hybrid gene on chromosome 22q plays a pivotal role in the pathogenesis of chronic myeloid leukemia ( CML ) , little is known of the reciprocal chimeric gene , ABL BCR , formed on chromosome 9q+ . ^^^ By reverse transcription / polymerase chain reaction amplification ( RT / PCR ) we have detected ABL BCR mRNA in cells from 31 of 44 BCR ABL positive CML patients and 3 of 5 CML cell lines . ^^^ ABL BCR expression consisted of ABL ( Ib ) BCR mRNA in 26 patients and of both ABL ( Ib ) BCR and ABL ( Ia ) BCR mRNA species in 6 patients . ^^^ The ABL BCR transcripts encoded one or , more rarely , both of the two potential junctions , designated ABL b 3 and ABL b 4 , which differed in size by 75 bp . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Retrovirally transduced antisense sequences stably suppress P210BCR ABL expression and inhibit the proliferation of BCR / ABL containing cell lines . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BCR ABL tyrosine kinase is autophosphorylated or transphosphorylates P 160 BCR on tyrosine predominantly within the first BCR exon . ^^^ Our previous studies demonstrated that P 210 BCR ABL co precipitates with P 160 BCR following immunoprecipitation with antibodies to the C terminal domain of P 160 BCR , sequences lacking in P 210 BCR ABL . ^^^ We now report that tryptic peptides shared by both P 160 BCR and P 210 BCR ABL are phosphorylated on tyrosine in vitro either when using immune complexes containing P 160 BCR complexed to BCR ABL or when P 160 BCR is phosphorylated in trans by P 210 BCR ABL immune complexes from cells lacking functional P 160 BCR . ^^^ P 185 BCR ABL produced in a cell line derived from a Ph chromosome positive acute lymphocytic leukemia patient also co immunoprecipitated with P 160 BCR . ^^^ As with P 210 BCR ABL , P 160 BCR tyrosine phosphopeptides were shared with P 185 BCR ABL , indicating that the major sites of tyrosine phosphorylation in vitro are contained within the first exon of P 160 BCR . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Induction of BCR ABL fusion genes by in vitro 10 irradiation . ^^^ The Philadelphia chromosome consists of a reciprocal translocation between the ABL oncogene at chromosome 9q34 and the BCR gene at chromosome 22q11 , resulting in the expression of chimeric BCR ABL mRNAs specific to chronic myelogenous leukemia ( CML ) . ^^^ Using this assay , it was possible to detect BCR ABL fusion genes induced among HL 60 cells after 100 Gy of 10 irradiation in vitro . ^^^ These fusion genes contained not only CML specific BCR ABL rearrangements , but also other forms of BCR ABL fusions . ^^^ These latter genes had junctions of BCR exon 4 / ABL exon 2 intervened by a segment of DNA of unknown origin , BCR exon 5 / ABL exon 2 , and BCR exon 4 / ABL exon 2 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
An actin binding function contributes to transformation by the Bcr Abl oncoprotein of Philadelphia chromosome positive human leukemias . ^^^ In Philadelphia chromosome positive human leukemias , which include chronic myelogenous leukemia and some acute lymphocytic leukemias , the c abl proto oncogene on chromosome 9 becomes fused to the bcr gene on chromosome 22 , and Bcr Abl fusion proteins are produced . ^^^ The Bcr sequences activate the Abl tyrosine kinase which is required for the transforming function of Bcr Abl . ^^^ The Bcr sequences also enhance an F actin binding activity associated with c Abl . ^^^ Here , we show that binding of c Abl and Bcr Abl proteins to actin filaments in vivo and in vitro is mediated by an evolutionarily conserved domain at the C terminal end of c Abl . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Comparison of baculovirus expressed c Abl and BCR / ABL protein tyrosine kinases . ^^^ Mouse c Abl type 4 and human BCR / ABL proteins have been expressed in insect cells using the baculovirus system . ^^^ They were identified by immunoprecipitation and immunoblotting with antibodies against ABL peptides and , for BCR / ABL , against a BCR peptide . ^^^ Partial purification could be achieved readily using ion exchange columns , and the BCR / ABL protein , p210BCR / ABL , could be further purified to near homogeneity using an antiphosphotyrosine column . ^^^ The oncogenic properties of p210BCR / ABL may be due to its different subcellular location , or to the presence of an intracellular inhibitor of c Abl that does not inhibit BCR / ABL , or to altered substrate specificity such that it can phosphorylate a unique substrate which is not recognised by c Abl . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We report the case of a patient having Philadelphia negative , bcr abl positive chronic myeloid leukemia . ^^^ In situ hybridization showed the presence of the bcr abl fusion on the chromosome 9 long arm in all mitoses observed . ^^^ Only three other patients with such presentation ( Philadelphia negative , bcr abl positive with bcr abl fusion on the chromosome 9 long arm ) have been reported , with a poor therapeutic response and outcome in two of them . ^^^ Translocation of BCR to chromosome 9 may therefore have a worse prognosis than translocation of ABL to chromosome 22 in Philadelphia negative chronic myeloid leukemia . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We examined the hybrid bcr / abl mRNA present in 59 patients with chronic myeloid leukemia , using the reverse transcription method and polymerase chain reaction . ^^^ Bcr / abl gene was found in 98 % of patients . 60 % of patients had b3a2 type of translocation , 40 % type b2a2 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The BCR gene is implicated in the development of Ph positive leukemia through its fusion with the nonreceptor tyrosine kinase gene ABL . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Cationic lipid mediated transfer of c abl and bcr antisense oligonucleotides to immature normal myeloid cells : uptake , biological effects and modulation of gene expression . ^^^ Uptake and biochemical and biological effects of antisense oligodeoxynucleotides ( ODN ) specific for c abl and bcr genes were studied in normal immature myeloid cells . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The 9 ; 22 chromosomal translocation in CML generates the bcr / abl fused gene coding P210bcr / abl that has enhanced tyrosine kinase activity . ^^^ However , blast crisis cells displayed enhanced the expression of bcr / abl mRNA , when compared with those in chronic phase cells . ^^^ The present study suggested one possibility that a selective and progressive process of Ph 1 clone with high expression of the bcr / abl gene may be involved with the transformation into non lymphoid crisis phases from chronic phases . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BCR ABL : an anti apoptosis gene in chronic myelogenous leukemia . ^^^ The expression of bcr abl in chronic myelogenous leukemia leads to a large increase in the generation of mature myeloid cells . ^^^ This up regulation in activity is mediated through the binding of a portion of the Bcr molecule to the SH 2 regulatory domain of the Abl protein . ^^^ This resistance can be overcome with the use of appropriate antisense oligonucleotides to the bcr abl gene . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The molecular genetic finding in these patients is the fused gene which developed by combination of the 3 ' part of the oncogene ABL from chromosome 9 and 5 ' part of the gene which developed by combination of the 3 ' part of the oncogene ABL from chromosome 9 and 5 ' part of the BCR `` gene ' ' . ^^^ Detection of BCR / ABL is an important diagnostic aid whic makes it possible to investigate residual diseases in patients after intensive treatment and transplantation of bone marrow and early detection of possible relapses . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Megakaryocytes carry the fused bcr abl gene in chronic myeloid leukaemia : a fluorescence in situ hybridization analysis from bone marrow biopsies . ^^^ The Ph translocation , fusing the abl and bcr genes on chromosomes 9 and 22 , however , obviously occurs as a second step in tumour development . ^^^ The question is whether the megakaryocytic cell lineage could harbour the bcr / abl fusion in those CML cases with striking proliferation of megakaryocytes but lack this genetic defect in cases with normal or decreased megakaryocyte counts . ^^^ We therefore performed triple colour fluorescence in situ hybridization ( FISH ) for portions of the bcr and abl genes flanking the breakpoint in CML in paraffin sections of CML cases with normal and with increased numbers of megakaryocytes . ^^^ This method allows identification of the bcr / abl fusion in single , morphologically intact cells , whereas conventional cytogenetics requires lysis and thus destruction of the cell . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
KBM 7 , a human myeloid leukemia cell line with double Philadelphia chromosomes lacking normal c ABL and BCR transcripts . ^^^ There was no evidence that normal BCR or c ABL messages were expressed , assessed with the reverse transcriptase polymerase chain reaction . ^^^ We conclude that the KBM 7 cell line will be of value for investigating molecular events underlying neoplastic transformation in CML , in particular for studying the effects of BCR ABL and ABL BCR on the proliferation of CML cells in the absence of normal BCR and c ABL messages . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Lack of correlation between ABL BCR expression and response to interferon alpha in chronic myeloid leukaemia . ^^^ Since the reciprocal ABL BCR gene is transcriptionally active in only a proportion of CML patients , it has been suggested that response to IFN alpha may correlate with ABL BCR expression . ^^^ In the present study we have tested 209 Ph positive CML patients for expression of ABL BCR , BCR ABL and the normal BCR and ABL genes by reverse transcriptase / polymerase chain reaction ( RT / PCR ) . ^^^ Whereas BCR ABL , BCR and ABL transcripts were detected in all the patients , ABL BCR expression was observed in 59 % of the cases . ^^^ The proportions of patients who were ABL BCR positive ( 63 % ) and ABL BCR negative ( 37 % ) were the same for good responders and poor responders , suggesting that there is no correlation between ABL BCR expression and cytogenetic response to IFN alpha in CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Intracellular processing of the products of the bcr abl junction region in CML Philadelphia chromosomes would generate novel peptides which , if they are capable of binding to HLA class 1 molecules , would be potential targets of a cytotoxic T cell response . ^^^ The 18 nonamers corresponding to the b 2 a2 and b 3 a2 fusions and differing from the parental bcr and abl sequences for at least one amino acid have been synthesized and tested for binding with HLA class 1 alpha chain preparations from HLA homozygous B lymphoblastoid cell lines . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Abnormal fusion of the BCR and ABL genes , resulting from the formation of the Philadelphia chromosome ( Ph ) , is the hallmark of Ph positive leukemia . ^^^ We have previously demonstrated that the Bcr protein is tyrosine phosphorylated within first exon sequences by the Bcr Abl oncoprotein . ^^^ Here we report that in addition to tyrose 177 ( Y 177 ) , Y 360 and Y 283 are phosphorylated in Bcr Abl proteins in vitro . ^^^ Moreover , Bcr tyrosine 360 is phosphorylated in vivo within both Bcr Abl and Bcr . ^^^ Tyrosine phosphorylated Bcr , phosphorylated in vitro by Bcr Abl , was greatly inhibited in its serine / threonine kinase activity , impairing both auto and transkinase activities of Bcr . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Detection of BCR / ABL fusion gene in CML : a preliminary report . ^^^ The BCR / ABL fusion gene in 31 patients with chronic myeloid leukemia ( CML ) was detected by RT / PCR . ^^^ In 8 cases of Ph ' negative patients , 4 had BCR 3 / ABL 2 rearrangement , 3 had both rearrangements while 1 had no BCR / ABL rearrangement . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
To test whether patients in remission after allogeneic bone marrow transplantation ( BMT ) possess a pool of chronic myeloid leukemia ( CML ) cells that do not express BCR ABL mRNA , we have compared the results and sensitivity of amplification of BCR ABL from genomic DNA with conventional reverse transcription polymerase chain reaction ( RT PCR ) . ^^^ Bubble PCR was used to amplify the genomic BCR ABL translocation breakpoints from chronic phase DNA of 10 patients with CML who subsequently underwent BMT . ^^^ After cloning and sequencing of the amplification products , patient specific ABL primers were synthesized and tested for both specificity and sensitivity in nested or heminested combinations with a variety of primers derived from the major breakpoint cluster region of the BCR gene . ^^^ In three samples from three patients , two of whom had been transplanted in the accelerated phase , PCR from genomic DNA was positive while RT PCR was negative ; this could mean that some CML cells in these samples had a reduced or absent capacity to express BCR ABL mRNA post transplant . ^^^ Because the great majority of samples ( 79 % ) gave concordant results with the two assays , we believe that patients in remission do not generally harbor a substantial pool of CML cells that do not express BCR ABL mRNA . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BCR rearrangement without juxtaposition of ABL in pre T acute lymphoblastic leukaemia . ^^^ However , fluorescence in situ hybridization ( FISH ) using BCR and ABL probes revealed a translocation with one breakpoint within the BCR gene on chromosome 22 without juxtaposition of ABL on chromosome 9 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Lineage involvement by BCR / ABL in Ph+ lymphoblastic leukemias : chronic myelogenous leukemia presenting in lymphoid blast vs Ph+ acute lymphoblastic leukemia . ^^^ Because it has been difficult to perform lineage studies of the Ph chromosome , we investigated the use of fluorescence in situ hybridization ( FISH ) with probes for BCR ( on chromosome 22 ) and ABL ( on chromosome 9 ) to study lineage involvement in Ph+ lymphoblastic malignancies . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Reverse transcriptase polymerase chain reaction for bcr / abl fusion in chronic myelogenous leukemia . ^^^ Using isolated total cellular RNA and a single primer pair , cDNA was transcribed , amplified , electrophoresed , and probed for bcr / abl fusion involving M bcr exons 2 and 3 of the bcr gene . ^^^ Of the RT PCR+ / Ph1 cases , most showed a weak but definite band by RT PCR , suggesting a low level of the bcr / abl fusion gene . ^^^ Our results indicate that RT PCR for detection of bcr / abl fusion is more sensitive than karyotyping in pre and post BMT samples . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
This method was shown to be applicable to other gene products by using primers specific for the abl and bcr genes . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Fluorescence in situ hybridization ( FISH ) and cytogenetic analysis were carried out in 33 transplanted patients suffering from different hematologic disease using probes for 10 and Y chromosomes and ABL and BCR genes . ^^^ It was concluded that FISH analysis is useful for : ( 1 ) characterizing cases in which standard cytogenetic analysis has failed ; ( 2 ) detecting host cells in sex mismatched transplanted patients ; and ( 3 ) evaluating Ph negative CML with the BCR / ABL rearrangement . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic myeloid leukaemia ( CML ) is characterized cytogenetically by a t ( 9 ; 22 ) ( q 34 ; ql 1 ) reciprocal translocation which gives origin to a hybrid BCR ABL gene , encoding a p2lO ( BCR ABL ) fusion protein with elevated tyrosine kinase activity and transforming abilities . ^^^ The t ( 9 ; 22 ) was suggested to be associated with genomic imprinting of centromeric regions of chromosomes 9 and 22 , but the genes directly affected by the translocation , ABL and BCR , were shown not to be imprinted . ^^^ For most diagnostic and research purposes the BCR ABL gene can be efficiently identified by reverse transcription and polymerase chain reaction ( RT / PCR ) amplification of its fusion transcripts , which can be quantified by competitive PCR and similar assays for assessment of residual disease in the follow up of therapy . ^^^ In the great majority of CML patients the BCR ABL transcripts exhibit a b2a2 and / or a b3a2 junction ; in rare cases , the only detectable BCR ABL transcripts have unusual junctions , such as b2a3 , b3a3 , e1a2 or e6a2 . ^^^ There is a recent suggestion that the BCR ABL gene may not be always ' functional ' , since extremely low levels of BCR ABL transcripts can be found in leucocytes from normal individuals and , conversely , it appears that no BCR ABL transcription can be detected in a proportion of Ph positive haematopoietic progenitors from some CML patients . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Kinetic selectivity of complementary nucleic acids : bcr abl directed antisense RNA and ribozymes . ^^^ In this work , we performed a systematic kinetic analysis to evaluate the selectivity of bcr abl directed antisense RNA and hammerhead ribozymes with a length of the complementary sequences of between 20 and 80 bases . ^^^ By kinetic in vitro selection , we identified oligomeric as well as long chain complementary RNA that annealed at least tenfold faster with the bcr abl sequence in comparison with either of the wild type sequences bcr or abl , respectively . ^^^ In the presence of selected oligodeoxynucleotide sequences and RNase H , the bcr abl transcript was specifically hydrolysed out of a mixture containing abl and bcr sequences as well . ^^^ Further , cleavage and binding occurred on opposite sides of the bcr abl fusion point . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Its molecular consequence is the genesis of a fusion gene BCR ABL between the 5 ' sequences of the BCR gene ( chromosome 22 ) and the 3 ' end of the ABL gene ( chromosome 9 ) . ^^^ Fluorescence in situ hybridization ( FISH ) using specific DNA probes provides a useful tool for the detection of t ( 9 ; 22 ) and BCR ABL rearrangement . ^^^ The cos bcr 51 and cos abl 18 probes that hybridize to unique sequences specific to the BCR and ABL genes have the ability to detect the BCR ABL rearrangement in metaphase cells as well as in interphase nuclei . ^^^ The BCR ABL rearrangement can be detected in metaphase spreads of insufficient quality or from interphase nuclei in the case of terminally differentiated cells or of cells which do not divide in vitro . ^^^ The FISH technique can also be used to detect the BCR ABL rearrangement in cases of Ph negative BCR ABL positive CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Essential thrombocythemia with BCR / ABL rearrangement . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Fluorescence in situ hybridization ( FISH ) technique has been successfully used to detect the BCR ABL gene fusion in chronic myeloid leukemia ( CML ) with the classic form of the Philadelphia chromosome ( Ph ) . ^^^ The results demonstrate that the use of a yeast artificial chromosome ( YAC ) derived probe ( D107F9 ) and a cosmid probe ( cos abl 8 ) , specific for BCR and ABL genes respectively , allows also the detection of the BCR ABL fusion in CML patients with variant Ph . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Duplication of chromosome 9 carrying a BCR / ABL chimeric gene in Philadelphia chromosome negative chronic myeloid leukemia . ^^^ In the chronic phase one chromosome 9 contained a BCR / ABL fusion gene instead of chromosome 22 . ^^^ Although in blast crisis , both chromosomes 9 had BCR / ABL fusion genes . ^^^ This may suggest that the critical event in CML is the formation of a BCR / ABL chimeric gene regardless of its locus in the genome . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Effects of BCR ABL antisense oligonucleotides ( AS ODN ) on human chronic myeloid leukemic cells : AS ODN as effective purging agents . ^^^ We examined phosphorothioate oligodeoxyribonucleotides ( ODNs ) directed against bcr in exon 3 or exon 2 , which are rearranged with exon 2 of abl ( B3A2 and B2A2 ) at t ( 9 ; 22 ) of chronic myelogenous leukemia ( CML ) . ^^^ In order to determine the ex vivo purging effects of bcr abl ODNs , the K 562 cells were mixed with PBSC from normal donors at a ratio of 1 : 20 ( CML : PBSC ) . ^^^ These results were confirmed by RT PCR using bcr abl primers and mRNA isolated from the mixture of cells . ^^^ Further , these results support the hypothesis that bcr abl antisense ODNs are potentially effective agents for ex vivo purging of autologous stem cells before transplantation to eliminate / reduce the burden of leukemic cells . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Elevated platelet count features the variant type of BCR / ABL junction in chronic myelogenous leukaemia . ^^^ A variant form of BCR / ABL junction was identified in a patient with chronic myelogenous leukaemia ( CML ) . ^^^ The BCR / ABL fusion mRNA of this patient showed in frame junction between BCR exon c 3 and ABL exon 2 . ^^^ The c 3 a2 type of BCR / ABL junction seems to be associated with elevated platelet count and thus could form a novel clinical entity different from typical CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
This growth promotion is dependent upon the structure of the amino terminus of the protein , and the ABL mutation will cooperate with certain BCR sequences in BCR / ABL fusion proteins to deregulate ABL kinase activity . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Analyses of BCR / ABL chimeric RNA by RT PCR method were negative in both of Major and Minor BCR / ABL chimeric RNA . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
This translocation juxtaposes parts of two genes ; ABL on chromosome 9 and BCR ( breakpoint cluster region ) on chromosome 22 . ^^^ Transcription of the BCR / ABL fusion gene results in an hybrid mRNA that is translated into a 210 kDa or 190 kDa protein , depending on the location of the breakpoint in the bcr region . ^^^ Nonetheless , the loss of the negative cell growth regulation by c ABL , or BCR / ABL fusion protein interaction with other cellular genes ( such as RAS or c MYC ) could also be involved in CML pathophysiology . ^^^ A better understanding of the molecular mecanisms of CML could lead to specific treatment , such as tyrosine kinase inhibitors , synthetic oligodeoxynucleotides , or site specific DNA binding proteins designed against BCR / ABL oncogenic fusion sequence . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BCR / ABL , p190BCR / ABL , and TEL / ABL activate similar signal transduction pathways in hematopoietic cell lines . ^^^ The Philadelphia chromosome translocation generates a chimeric oncogene , BCR / ABL which causes chronic myelogenous leukemia . ^^^ Two different fusion proteins can be produced , p190BCR / ABL and p210BCR / ABL , depending on the location of the breakpoint in BCR . ^^^ Although the ABL tyrosine kinase activity of the resulting oncoprotein is essential for transformation , the exact functional contribution of BCR to transformation is unclear . ^^^ These results suggest that the function of BCR can be largely replaced by the unrelated protein TEL with regards to transformation of murine hematopoietic cell lines to factor independence , and support the hypothesis that a major contribution of both fusion partners is to activate the ABL tyrosine kinase . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
A novel BCR ABL fusion gene ( e6a2 ) in a patient with Philadelphia chromosome negative chronic myelogenous leukemia . ^^^ A novel variant of the chimeric BCR ABL mRNA transcript was detected in a patient with Philadelphia chromosome negative ( Ph ) chronic myelogenous leukemia ( CML ) by multiplex reverse transcription polymerase chain reaction ( RT PCR ) . ^^^ Sequence analysis of the fusion region of the amplified cDNA fragment showed an in frame joining of exon e 6 of the BCR gene and exon a 2 of the ABL gene , giving rise to an e6a2 BCR ABL transcript . ^^^ Western blot studies detected a BCR ABL protein slightly larger than p 185 BCR ABL . ^^^ Metaphase fluorescence in situ hybridization showed an insertion of ABL material into the BCR region without reciprocal BCR translocation . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Investigating and improving the specificity of ribozymes directed against the bcr abl translocation . ^^^ Chronic myelogenous leukaemia ( CML ) is associated with a translocation between the ABL and BCR genes on chromosomes 9 and 22 , t ( 9 ; 22 ) . ^^^ The resulting transcription and translation products , bcr abl mRNA and p210bcr abl , are unique to the malignant cells and as such are ideal targets for specific chemicals or drugs . ^^^ We have designed hammerhead ribozymes to cleave the two predominant forms of bcr abl mRNA , b2a2 and b3a2 . ^^^ Synthetic bcr abl RNA substrates were cleaved by the ribozymes in vitro , but so was a wild type abl RNA sequence . bcr RNA was not cleaved in vitro and mutant ribozymes showed no cleavage activity . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The influence of class 2 HLA type on the lymphoproliferative response of normal donors to a bcr abl fusion peptide . ^^^ Chronic myelogenous leukemia ( CML ) is characterized by a t ( 9 ; 22 ) chromosomal translocation resulting in the expression of a novel bcr abl fusion protein . ^^^ This gave a mean stimulation index of 2 . 73 ( 95 % CI 2 . 42 3 . 05 ) and 50 / 54 ( 93 % ) of donors gave responses that were greater than those with bcr or abl control peptides . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Are ABL and BCR imprinted . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Sequences within the first exon of BCR inhibit the activated tyrosine kinases of c Abl and the Bcr Abl oncoprotein . ^^^ The Bcr Abl oncoprotein is the primary causative factor in Philadelphia chromosome associated leukemias . ^^^ The activated tyrosine kinase of the Bcr Abl oncoprotein is the primary driving force behind its oncogenic activity . ^^^ We report here that a deleted form of Bcr [ Bcr ( 64 413 ) ] , encompassing the Abl SH 2 binding domains of Bcr , reduced the phosphotyrosine content of c Abl and Bcr Abl within cells and inhibited Bcr Abl autophosphorylation activity in vitro . ^^^ Similarly , a Bcr peptide phosphorylated on Ser 354 blocked the c Abl and Bcr Abl kinases in vitro , whereas the same peptide phosphorylated on Tyr 360 was not inhibitory . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
To test whether the functional loss of p 53 plays a direct role in the transition of chronic phase to blast crisis , bone marrow cells from p53+ / + or p 53 / mice were infected with a retrovirus carrying either the wild type BCR / ABL or the inactive kinase deficient mutant , and were assessed for colony forming ability . ^^^ Infection of p 53 / marrow cells with wild type BCR / ABL , but not with the kinase deficient mutant , enhanced formation of hematopoietic colonies and induced growth factor independence at high frequency , as compared with p53+ / + marrow cells . ^^^ These effects were suppressed when p 53 / marrow cells were coinfected with BCR / ABL and wild type p 53 . p 53 deficient BCR / ABL infected marrow cells had a proliferative advantage , as reflected by an increase in the fraction of S+G2 phase cells and a decrease in the number of apoptotic cells . ^^^ Immunophenotyping and morphological analysis revealed that BCR / ABL positive p 53 / cells were much less differentiated than their BCR / ABL positive p53+ / + counterparts . ^^^ Injection of immunodeficient mice with BCR / ABL positive p 53 / cells produced a transplantable , highly aggressive , poorly differentiated acute myelogenous leukemia . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Cytogenetic and molecular genetic studies were performed to resolve the status of BCR and ABL in the bone marrow or peripheral blood cells of the two CML patients with complex translocations involving chromosomes 3 , 9 , 22 and 9 , 12 , 22 respectively . ^^^ In the first case the presence of Ph chromosome was detected cytogenetically , BCR ABL translocation was detected by Southern hybridization . ^^^ In the second case , only the PCR method showed BCR ABL rearrangement . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Treatment of Philadelphia leukemia in severe combined immunodeficient mice by combination of cyclophosphamide and bcr / abl antisense oligodeoxynucleotides . ^^^ BACKGROUND : Philadelphia cells are human chronic myelogenous leukemia ( CML ) cells that contain the BCR / ABL oncogene ( a fusion of the BCR and ABL genes ) . ^^^ Selective eradication of these cells in vitro can be achieved by combined treatment with antisense phosphorothioate oligodeoxynucleotides ( [ S ] ODNs ) specifically targeted to this oncogene ( bcr / abl [ S ] ODNs ) and a suboptimal ( for use as a single agent ) dose of mafosfamide ( the in vitro active form of cyclophosphamide ) . ^^^ PURPOSE : We evaluated the ability of bcr / abl antisense [ S ] ODNs , alone or subsequent to treatment with a single injection of cyclophosphamide , to suppress the leukemic process induced in severe combined immunodeficient ( SCID ) mice by Philadelphia cells ( i . e . , primary CML blast crisis [ CML BC ] cells ) . ^^^ In addition , we studied potential mechanisms that might explain the efficacy of the bcr / abl antisense [ S ] ODN mafosfamide combination against Philadelphia cells in vitro . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The presence of the bcr / abl chimeric gene was detected by fluorescent in situ hybridization ( FISH ) using differently labelled bcr and abl specific probes . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
To gain insight into the sensitivity and specificity of the detection of the bcr / abl translocation by FISH , a group of 10 healthy volunteers was also studied . ^^^ Our results show that for the detection of bcr / abl translocation in CML patients , FISH is more sensitive than conventional cytogenetics because it detects significantly higher proportions of cells carrying the translocation both in metaphase ( P < . 0002 ) and interphase nuclei ( P < . 003 ) . ^^^ Moreover , in the metaphases of the controls analyzed , no bcr / abl+ chromosome was detected that makes the colocalization of bcr and abl signals in the CML patients highly specific . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic myelogenous leukemia expressing two bcr abl chimeric mRNA ; a case report ] . ^^^ Chronic myelogenous leukemia ( CML ) expresses two types of bcr abl chimeric mRNA . ^^^ One is b3a2 type in which bcr exon 3 binds to abl exon 2 , the other is b2a2 type that bcr exon 2 binds to abl exon 2 . ^^^ Either bcr abl is normally expressed , but both types of bcr abl mRNA can be expressed at the same time in a patient . ^^^ We report here a rare case of CML expressing two types of bcr abl mRNA and discuss the possibility that this double expression would help to monitor the clinical course of CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
A novel acute lymphoid leukaemia type BCR / ABL transcript in chronic myelogenous leukaemia . ^^^ Using a reverse transcription polymerase chain reaction ( RT PCR ) , we identified a patient with typical clinical features of chronic myelogenous leukaemia ( CML ) in the chronic phase who showed no amplification of the CML type BCR / ABL transcript . ^^^ Sequencing revealed the novel transcript to be a chimaeric mRNA produced by fusion of a segment of BCR exon 2 ( e 2 ) to ABL exon 2 ( a 2 ) , with a 21 base pair insertion of ABL intron 1b sequence between them . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The most common genetic tests for CGL include quantitative cytogenetic studies , fluorescence in situ hybridization with probes for BCR and ABL , Southern blot analysis , and reverse transcriptase polymerase chain reaction . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
FISH analysis , using two chromosome painting probes and a BCR / ABL specific probe , confirmed the cytogenetic observation of a 22q11 . 2 > 4p14 and a 4p14 > 9q34 exchange , and revealed the presence of a 9q34 > 22q11 . 2 , respectively . ^^^ In addition , RT PCR demonstrated the presence of a BCR / ABL transcript derived from the major breakpoint cluster region ( M bcr ) of the BCR gene . ^^^ Because the presentation of AML with this ABL > BCR fusion product is a rare event , it would seem likely that the additional complex chromosomal rearrangement involving chromosomes 4 , 9 , and 22 played a role in the aggressive presentation and clinical behavior of this patient ' s leukemia . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Factors influencing the false positive and negative rates of BCR ABL fluorescence in situ hybridization . ^^^ BCR ABL fluorescence in situ hybridization has a useful role to play in experimental and clinical investigations of chronic myeloid leukaemia . ^^^ We established two different criteria for BCR ABL positivity : by criterion A cells were scored as positive when BCR and ABL signals were overlapping or touching and by criterion B cells were positive if they satisfied criterion A or if the signals were separated by up to one signal diameter . ^^^ We conclude that these factors should be considered when evaluating the results of FISH studies to detect the BCR ABL fusion gene and that analogous factors may influence results of FISH studies directed at other fusion genes . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BCR ABL is a chimaeric oncogene generated by translocation of sequences from the c ABL protein tyrosine kinase gene on chromosome 9 into the BCR gene on chromosome 22 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The function of BCR / ABL and related proto oncogenes . ^^^ The BCR / ABL oncogene product is one of the genes associated with and possibly responsible for human leukemias . ^^^ The possibilities are also discussed that inhibition of apoptosis and altered adhesive properties to the bone marrow microenvironment by BCR / ABL might contribute to disease initiation . . ^^^ In this article , recent advances in understanding the function of these oncogenes as well as the function of normal counterparts , c Abl and Bcr , are discussed . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Clinical use of the bcr / abl probe test in the evaluation of chronic myeloid leukemia patients . ^^^ CML is characterized by a reciprocal translocation between the abl and bcr genes on chromosomes 9 and 22 and is usually diagnosed by the presence of the Philadelphia ( Ph 1 ) chromosome . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Neutrophilic chronic myeloid leukemia : a distinct disease with a specific molecular marker ( BCR / ABL with C3 / A2 junction ) . ^^^ We have analyzed the genomic DNA by Southern blotting and the BCR / ABL hybrid gene transcripts by reverse transcriptase polymerase chain reaction in three patients with clinical findings of CML N , who did have a t ( 9 ; 22 ) chromosomal translocation . ^^^ In all patients we have found a rare type of BCR / ABL rearrangement , with a breakpoint between exons c 3 and c 4 of the BCR gene ( corresponding to BCR exons 19 and 20 ) . ^^^ This type of junction causes almost the entire BCR gene to fuse with ABL . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
This chromosome arises from the t ( 9 ; 22 ) ( q 34 ; q 11 ) translocation which results in the juxtaposition of the bcr gene and the abl proto oncogene . ^^^ This BCR / ABL fusion gene encodes for a hybrid protein with the capacity of oncogenic transformation of hematopoietic cells . ^^^ Half of these Ph negative CML have the BCR / ABL fusion gene ( BCR positive ) and are considered equivalent to Ph positive CML . ^^^ In contrast , the patients without detectable BCR / ABL fusion ( BCR negative ) fulfil the criteria for atypical CML ( aCML ) of the French American British ( FAB ) classification , despite considerable variability at the individual level . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In this study , patients with Philadelphia ( Ph ) negative and positive chronic myelogenous leukemia ( CML ) were analyzed by unicolor and dual color ( DC ) fluorescence in situ hybridization ( FISH ) using abl and bcr cosmid probes . ^^^ Unicolor and DC FISH analysis revealed a BCR ABL fusion in a Ph negative patient . ^^^ DC FISH to interphase nuclei revealed the BCR ABL fusion , even though no metaphases were available for metaphase FISH and conventional cytogenetic analysis . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Another study used probes for bcr and abl to detect bcr / abl fusion in interphase nuclei in chronic myelogenous leukemia . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We and others have shown that the Bcr Abl oncoprotein binds activators of the Ras pathway such as Grb 2 and Shc . ^^^ Our results indicate that P 160 BCR is tyrosine phosphorylated at the same site by Bcr Abl in kinase assays ( Puil et al . , 1994 ) . ^^^ We performed experiments to determine whether Bcr , which was tyrosine phosphorylated within cells by activated c Abl , could also bind Grb 2 , and whether phosphotyrosine 177 was the major binding site . ^^^ Complexes between Bcr and Abl were detected in a hemopoietic cell line lacking Bcr Abl and in COS 1 cells coexpressing both Bcr and Abl proteins . ^^^ P 160 BCR was tyrosine phosphorylated in COS 1 cells coexpressing Abl and Bcr proteins . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Prognostic significance of BCR ABL rearrangement in chronic myeloid leukemia . ^^^ At the molecular level , this translocation results in the activation of the ABL oncogene of chromosome 9 , which becomes contiguous with the 5 ' end of the BCR gene on chromosome 22 . ^^^ The aim of the present study was to characterize the type of BCR ABL transcript in 32 patients with CML using the reverse transcriptase polymerase chain reaction ( RT PCR ) and to determine if this type of rearrangement is related to the survival of the patients . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Distribution of ABL and BCR genes in cell nuclei of normal and irradiated lymphocytes . ^^^ Using dual color fluorescence in situ hybridization ( FISH ) combined with two dimensional ( 2D ) image analysis , the locations of ABL and BCR genes in cell nuclei were studied . ^^^ The center of nucleus to gene and mutual distances of ABL and BCR genes in interphase nuclei of nonstimulated and stimulated lymphocytes as well as in lymphocytes stimulated after irradiation were determined . ^^^ We found that , after stimulation , the ABL and BCR genes move towards the membrane , their mutual distances increase , and the shortest distance between heterologous ABL and BCR genes increases . ^^^ The distribution of the shortest distances between ABL and BCR genes in the G 0 phase of lymphocytes corresponds to the theoretical distribution calculated by the Monte Carlo simulation . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
HLA DR 1 restricted bcr abl ( b3a2 ) specific CD4+ T lymphocytes respond to dendritic cells pulsed with b3a2 peptide and antigen presenting cells exposed to b3a2 containing cell lysates . ^^^ Chronic myeloid leukemia ( CML ) is characterized by a specific translocation of the c abl oncogene on chromosome 9 to the break point cluster region ( bcr ) on chromosome 22 , t ( 9 ; 22 ) ( q 34 ; q 11 ) . ^^^ This translocation results in the expression of a 210 kD bcr abl protein fusion gene product . ^^^ The juxtaposition of the bcr and abl genes produces a novel junctional amino acid sequence , which may be presented by antigen presenting cells and recognized specifically by human T lymphocytes . ^^^ We also show that bcr abl , b3a2 peptide specific T lymphocyte lines proliferate in response to bcr abl b3a2 containing cell lysates ( K 562 or CML PBMC derived ) but not control ( including b2a2 CML PBMC ) lysates . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Sequential interphase FISH analysis of m BCR / ABL chimeric gene positive cells in Ph positive acute myeloid leukemia . ^^^ We report a case of Philadelphia ( Ph ) positive AML in which interphase fluorescence in situ hybridization ( FISH ) analysis was performed from diagnosis throughout the course of therapy using major ( M ) breakpoint cluster region ( BCR ) / minor ( m ) BCR and ABL cosmid probes . ^^^ We detected the m BCR / ABL fusion gene by interphase FISH analysis using an m BCR / ABL translocation probe , and found that FISH analysis was useful for classifying the BCR , identifying minimal residual disease , and for predicting imminent relapse after chemotherapy and PBSCT . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Improved sensitivity of BCR ABL detection : a triple probe three color fluorescence in situ hybridization system . ^^^ As a result of the Ph translocation , parts of the ABL and BCR genes become fused . ^^^ Fluorescence in situ hybridization ( FISH ) with probes from the BCR and ABL regions can also identify the Ph translocation in interphase cells . ^^^ This system was used to determine the frequency of interphase cells carrying the BCR ABL fusion gene in bone marrow and peripheral blood granulocytes from patients showing variable cytogenetic responses to interferon . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Variant Philadelphia translocation t ( 9 ; 17 ) ( q34 . 2 3 ; q21 . 3 ) with colocalization of the BCR and ABL genes on chromosome 9 in chronic myeloid leukemia . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
A Ph negative chronic myeloid leukemia patient with a non classical BCR ABL rearrangement characterized by fluorescence in situ hybridization . ^^^ A patient with chronic myeloid leukemia ( CML ) , a normal karyotype and a BCR ABL rearrangement is presented . ^^^ Fluorescence in situ hybridization ( FISH ) with an ABL probe ( 9q34 . 2 ) and an Mbcr probe ( 22q11 ) showed ABL and BCR signals on chromosome 22 . ^^^ The absence of ABL BCR gene expression in this and other patients described in the literature with this subtype of Ph negative CML , does not seem to have an impact on the clinical course of the disease . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Comparison of the specificities and catalytic activities of hammerhead ribozymes and DNA enzymes with respect to the cleavage of BCR ABL chimeric L 6 ( b2a2 ) mRNA . ^^^ With the eventual goal of developing a treatment for chronic myelogenous leukemia ( CML ) , attempts have been made to design hammerhead ribozymes that can specifically cleave BCR ABL fusion mRNA . ^^^ In the case of L 6 BCR ABL fusion mRNA ( b2a2 type ; BCR exon 2 is fused to ABL exon 2 ) , which has no effective cleavage sites for conventional hammerhead ribozymes near the BCR ABL junction , it has proved very difficult to cleave the chimeric mRNA specifically . ^^^ Therefore , we explored the possibility of using newly selected DNA enzymes that can cleave RNA molecules with high activity to cleave L 6 BCR ABL fusion ( b2a2 ) mRNA . ^^^ Cleavage occurred only within the abnormal BCR ABL mRNA , without any cleavage of the normal ABL or BCR mRNA . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BCR / ABL negative progenitors are enriched in the adherent fraction of CD34+ cells circulating in the blood of chronic phase chronic myeloid leukemia patients . ^^^ Expression of p 210 BCR / ABL mRNA by adherent , non adherent , HLA DR ( hi ) and HLA DR ( lo ) CD34+ cell subpopulations was demonstrated by RT PCR . ^^^ Using fluorescence in situ hybridization ( FISH ) in conjunction with BCR and ABL probes we detected Ph+ and Ph cells in both adherent and non adherent CD34+ cell fractions of 15 / 15 patients studied and in the HLA DR ( lo ) or CD 38 ( lo ) sorted CD34+ cell fractions . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The BCR / ABL oncogene encodes an activated tyrosine kinase that causes human chronic myelogenous leukemia . ^^^ One of the important contributions of BCR to transformation is believed to be dimerization or oligomerization of ABL , thereby activating ABL tyrosine kinase activity . ^^^ The major target proteins have been identified , and are very similar to the known substrates of BCR / ABL , including Shc , CBL , CRKL , and several proteins in the cytoskeleton . ^^^ EPO treatment also resulted in biological effects that were remarkably similar to those of BCR / ABL , including improved viability , altered integrin function , and a weak mitogenic signal . ^^^ This ligand regulatable oncogene mimics some of the biological effects of BCR / ABL , and analysis of ABL mutants in this system will be useful to dissect the signaling pathways that cause CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BCR / ABL transcripts and leukemia phenotype : an unsolved puzzle . ^^^ Although its molecular counterpart is always represented by a rearrangement between the BCR and the ABL genes , this shows a certain degree of molecular variability . ^^^ However , a number of old and more recent observations seem to suggest that not only qualitative differences in the type of BCR / ABL proteins expressed , but also quantitative variations in their total level within the cells may have an important role in determining the leukemia phenotype . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Philadelphia like translocation t ( 9 ; 22 ) ( q 34 ; q 11 ) found in a follicular lymphoma involving not BCR and ABL but IGL mediated rearrangement of an unknown gene on 9q34 . ^^^ Two color fluorescence in situ hybridization ( FISH ) with ABL and BCR probes revealed presence of a `` fusion ' ' signal , but its atypical localization [ der ( 9 ) ] and gene order [ cen ABL BCR tel ] indicated that this translocation differed from the t ( 9 ; 22 ) in chronic myeloid leukemia and did not involve either ABL or BCR . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The chimeric BCR ABL gene . ^^^ The 1982 discovery that in chronic myeloid leukaemia ( CML ) the ABL proto oncogene is translocated to the BCR gene located on chromosome 22 initiated many studies on the structural organization and function of these genes . ^^^ The nucleotide sequence of the entire BCR and major parts of the ABL gene has now been determined . ^^^ However , the actual cause of the fusion of BCR with ABL remains essentially unknown . ^^^ Mouse models have been helpful to unravel the normal cellular function of BCR and ABL , as well the activity of BCR ABL , although a single mechanism explaining the transforming activity of the latter has not been discovered . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Localisation and distance between ABL and BCR genes in interphase nuclei of bone marrow cells of control donors and patients with chronic myeloid leukaemia . ^^^ Quantitative measurements of the nuclear localisation of the ABL and BCR genes and the distance between them were performed in randomly oriented bone marrow cells of control donors and patients with chronic myeloid leukaemia ( CML ) . ^^^ Most ABL and BCR genes ( 75 % ) are located at a distance of 20 65 % of the local radius from the nuclear centre to the nuclear membrane . ^^^ A chimeric BCR ABL gene located on a derivative chromosome 22 resulting from t ( 9 ; 22 ) ( q 34 ; q 11 ) [ the so called Philadelphia ( Ph ) chromosome ] as well as the intact ABL and BCR genes of patients suffering from chronic myeloid leukaemia are also located mostly in this region , which has a mean thickness of 2 microns in bone marrow cells . ^^^ The minimum distance between one ABL and one BCR gene is less than 1 micron in 47 . 5 % of bone marrow cells of control donors . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The tyrosine kinase inhibitor CGP57148B selectively inhibits the growth of BCR ABL positive cells . ^^^ The Philadelphia chromosome found in virtually all cases of chronic myeloid leukemia ( CML ) and in about one third of the cases of adult acute lymphoblastic leukemia is formed by a reciprocal translocation between chromosomes 9 and 22 that results in the fusion of BCR and ABL genetic sequences . ^^^ This BCR ABL hybrid gene codes for a fusion protein with deregulated tyrosine kinase activity that can apparently cause malignant transformation . ^^^ CGP57148B , a 2 phenylaminopyrimidine derivative , has been shown to selectively inhibit the tyrosine kinase of ABL and BCR ABL . ^^^ However , almost all CML colonies that grow in the presence of 1 . 0 micromol / L CGP57148B are BCR ABL positive , which may reflect the fact that residual normal clonogenic myeloid precursors are infrequent in most patients with CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Philadelphia ( Ph ) chromosome formation results in the relocation of the ABL oncogene from the chromosome 9q34 to BCR region on 22q11 , forming the BCR / ABL fusion gene . ^^^ Fluorescence in situ hybridization detected residual BCR / ABL positive interphase cells during the 12th month of therapy . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Fluorescence in situ hybridization ( FISH ) analyses chromosomes to detect either the juxtaposition of BCR and ABL sequences or the disruption of these genes ; Southern blotting analyses genomic DNA to determine whether the BCR gene is rearranged ; reverse transcriptase polymerase chain reaction ( RT PCR ) analyses RNA to determine the presence or absence of BCR ABL transcripts ; Western blotting analyses cell lysates to determine the presence or absence of BCR ABL protein . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The Src family kinase Hck interacts with Bcr Abl by a kinase independent mechanism and phosphorylates the Grb 2 binding site of Bcr . bcr abl , the oncogene causing chronic myeloid leukemia , encodes a fusion protein with constitutively active tyrosine kinase and transforming capacity in hematopoietic cells . ^^^ Various intracellular signaling intermediates become activated and / or associate by / with Bcr Abl , including the Src family kinase Hck . ^^^ To elucidate some of the structural requirements and functional consequences of the association of Bcr Abl with Hck , their interaction was investigated in transiently transfected COS 7 cells . ^^^ Neither the complex formation of Hck kinase with Bcr Abl nor the activation of Hck by Bcr Abl was dependent on the Abl kinase activity . ^^^ Both inactivating point mutations of Hck and dephosphorylation of Hck enhanced its complex formation with Bcr Abl , indicating that their physical interaction was negatively regulated by Hck ( auto ) phosphorylation . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
A comparative analysis of FISH , RT PCR , and cytogenetics for the diagnosis of bcr abl positive leukemias . ^^^ Philadelphia ( Ph ) chromosome positive leukemias , with the bcr abl gene translocation , have a dismal prognosis . ^^^ Reverse transcriptase polymerase chain reaction ( RT PCR ) analysis is considered the most sensitive tool for the detection of the bcr abl translocation , and it is widely used alone or in combination with karyotyping or Southern blot analysis to identify Ph positive cases . ^^^ In this study , we used fluorescence in situ hybridization ( FISH ) with BCR and ABL double color probes for detecting Ph positive leukemias . ^^^ FISH analysis proved to be simple , extremely reliable and sensitive ; bcr abl fusion detection was successful in the presence of all types of molecular junctions i . e . , ( b2a2 , b3a2 , and e1a2 ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Assessment of differential engraftment of normal and leukemic cells by fluorescence in situ hybridization analysis with bcr and abl probes showed that a median of 35 % ( range , 5 % to 91 % ) of engrafted cells present in the murine BM were leukemic . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Direct in cell amplification of the breakpoint cluster region ( BCR ) Abelson ( ABL ) fusion transcript of chronic myeloid leukemia ( CML ) has recently been accomplished in Italy using bone marrow mononuclear cell suspensions . ^^^ Satisfactory amplification of the BCR ABL fusion transcript occurred , and distinct blue cytoplasmic granules that varied in intensity were found in most CML blasts . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BCR ABL activates pathways mediating cytokine independence and protection against apoptosis in murine hematopoietic cells in a dose dependent manner . ^^^ The hallmark of chronic myeloid leukemia ( CML ) is the chimeric tyrosine kinase oncogene bcr abl . ^^^ Since expression of bcr abl mRNA frequently increases with disease progression and a duplication of the Philadelphia chromosome ( harbouring the bcr abl hybrid locus ) represents the most frequent karyotypic abnormality in acute phase CML , we hypothesized that the level of BCR ABL protein may affect the disease phenotype . ^^^ Therefore , the biological effects of high and low levels of BCR ABL expression were compared in growth factor dependent and independent myeloid and lymphoid cell lines . ^^^ Our results demonstrated that low levels of BCR ABL were sufficient to render these cell lines growth factor independent and tumorigenic , but higher levels were mandatory for additional protection against apoptotic stimuli . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
A Philadelphia negative chronic myelogenous leukemia with the chimeric BCR / ABL gene on chromosome 9 and a b 3 a2 splice junction . ^^^ The BCR / ABL rearrangement was detected by reverse transcriptase polymerase chain reaction and Southern blotting analysis , which suggested a b 3 a2 splice junction . ^^^ Dual color fluorescence in situ hybridization ( FISH ) with BCR and ABL DNA probes showed that the chimeric fusion gene was localized on chromosome 9q34 , rather than at the typical location on chromosome 22q11 . ^^^ The BCR / ABL rearrangement was detected in 75 % of the patient ' s bone marrow population , whereas the remaining 25 % of the cells appeared normal . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Detection of bcr / abl fusion transcripts by semiquantitative multiplex RT PCR combined with a colormetric assay in Ph positive leukemia . ^^^ We studied the feasibility of the clinical application of a new bcr / abl analysis system , C TRAK t ( 9 ; 22 ) , consisting of a multiplex RT PCR and a colormetric assay . ^^^ With this system , bcr / abl transcripts could be detected in all of 24 cytogenetic Philadelphia chromosome ( Ph ) positive leukemia patients and in none of eight Ph negative patients . ^^^ Multiple bcr / abl transcripts could be detected in three of the 24 Ph positive patients , the fusion of bcr exon 1 to abl exon 2 ( e1a2 junction ) dominated that of bcr exon 13 to abl exon 2 ( b2a2 junction ) in two cases and that of bcr exon 14 to abl exon 2 ( b3a2 junction ) and b2a2 dominated e1a2 in one case . ^^^ This system was sensitive enough to be able to detect even one bcr / abl transcript producing cell in 50000 bcr / abl negative background cells , thus making it suitable for semiquantitative evaluation . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Evidence for specific immune response against P 210 BCR ABL in long term remission CML patients treated with interferon . ^^^ Total peripheral blood mononuclear cells ( PBMCs ) from CML patients in long term remission following interferon treatment exhibited significantly higher proliferative responses ( four to 15 fold over background ) than normals directed against P 210 BCR ABL in extracts of transfected monkey fibroblast cells . ^^^ Surprisingly , similar enhanced levels of specific proliferative responses were observed with extracts from cells expressing Bcr and / or Abl proteins . ^^^ Control monkey fibroblast cells lacking BCR ABL expression failed to induce proliferation over background levels . ^^^ Normal individuals had no significant responses to Bcr / Abl extracts . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
A novel BCR ABL rearrangement in a Philadelphia chromosome positive chronic myelogenous leukaemia variant with thrombocythaemia . ^^^ Reverse transcription polymerase chain reaction was used to detect an unusual BCR / ABL transcript in a patient who presented with thrombocythaemia and was Philadelphia chromosome positive but weakly reactive to conventional BCR / ABL fusion probes . ^^^ Sequencing revealed the presence of a 12 bp insert between BCR exon 2 ( b 2 ) and ABL exon 2 ( a 2 ) . ^^^ In such cases the use of conventional BCR / ABL probes may lead to false negative results . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Bcl 2 independent Bcr Abl mediated resistance to apoptosis : protection is correlated with up regulation of Bcl xL . ^^^ Bcr Abl is the molecule responsible for both the transformation phenotype and the resistance to chemotherapeutic drugs found in chronic myelogenous leukemia ( CML ) cells . ^^^ We show here that expression of Bcr Abl in HL 60 cells rendered them extremely resistant to apoptosis induced by a wide variety of agents . ^^^ The anti apoptotic effect of Bcr Abl was found to be independent of the phase of the cell cycle . ^^^ Treatment with antisense oligonucleotides directed to bcr decreased the expression of the ectopic bcr abl and restored susceptibility to apoptosis . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Extramedullary presentation of chronic myelogenous leukemia with p 190 BCR / ABL transcripts . ^^^ We present here a rare case of Philadelphia chromosome ( Ph ) positive chronic myelogenous leukemia having p 190 BCR / ABL with a malignant clinical picture of extramedullary blast crisis at onset , followed by rapid evolution to bone marrow blast crisis . ^^^ The present case suggests that p 190 BCR / ABL is associated with the aggressive course of the disease . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The BCR gene recombines preferentially with Alu elements in complex BCR ABL translocations of chronic myeloid leukaemia . ^^^ Chronic myeloid leukaemia ( CML ) develops when two genes , BCR on chromosome 22 and ABL on chromosome 9 , recombine to form a hybrid BCR ABL gene with leukaemogenic properties . ^^^ The mechanism which underlies this recombination is unknown , but additional chromosome sites may be involved to form complex BCR ABL rearrangements . ^^^ Here , we show that the 3 ' part of M Bcr recombined within , or immediately adjacent to , Alu elements at the additional sites in all five complex BCR ABL rearrangements that have been examined so far . ^^^ This is a new finding which suggests that Alu sequences have an affinity for the BCR ABL recombination process in complex rearrangements , and provides additional evidence for the association of these elements with somatic rearrangements which cause human leukaemia . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Comparison of activities between hammerhead ribozymes and DNA enzymes targeted to L 6 BCR ABL chimeric ( b2a2 ) mRNA . ^^^ For the treatment of chronic myelogenous leukemia ( CML ) , attempts have been made to design hammerhead ribozymes that can specifically cleave BCR ABL fusion mRNA . ^^^ In the case of L 6 BCR ABL fusion mRNA ( b2a2 type ) , which has no effective cleavage sites for conventional hammerhead ribozymes near the BCR ABL junction , it has proved very difficult to cleave the chimeric mRNA specifically . ^^^ Therefore , we explored the possibility of using DNA enzymes , that was newly selected by Santoro & Joyce and that can cleave RNA molecules with high activity , to cleave of L 6 BCR ABL fusion ( b2a2 ) mRNA . ^^^ By contrast to the results with the conventional ribozymes , the newly designed DNA enzymes , having higher flexibility for selection of cleavage sites , were able to cleave this chimeric RNA molecule specifically at sites close to the junction , without any cleavage of the normal ABL or BCR mRNA . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Bcr / Abl associated leukemogenesis in bcr null mutant mice . ^^^ The BCR gene contributes to Philadelphia positive leukemogenesis via a number of discrete mechanisms , one of which may be through interaction of its normal gene product with the Bcr / Abl oncoprotein . ^^^ In the current study this hypothesis was tested in vivo by introducing a Bcr / Abl P 190 transgene into mice lacking endogenous bcr protein . ^^^ Our finding , that the P 190 BCR / ABL oncogene is still capable of producing leukemia in these mice with indistinguishable latency and clinical pattern as in genetically matched counterparts , rules out any significant or major contribution of the bcr protein as a whole to leukemia development in these mice . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Role of the adapter protein CRKL in signal transduction of normal hematopoietic and BCR / ABL transformed cells . ^^^ CRKL is a prominent substrate of the BCR / ABL oncoprotein in chronic myelogenous leukemia and binds to both BCR / ABL and c ABL . ^^^ Structurally , the amino terminal SH 3 domain of CRKL has been shown to bind proteins such as C3G , SOS , PI 3 K , c ABL or BCR / ABL . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Importance of mixed chimerism to predict relapse in persistently BCR / ABL positive long survivors after allogeneic bone marrow transplantation for chronic myeloid leukemia . ^^^ Determination of hematological chimerism could be helpful in understanding the biology of leukemic relapse after allogeneic bone marrow transplant ( BMT ) for chronic myeloid leukemia ( CML ) , because the detection of malignant residual cells carrying the bcr / abl message by qualitative RT PCR is of limited value in predicting disease progression for individual patients . ^^^ We have studied the chimerism pattern and the bcr / abl status by Southern blot in 15 CML patients ( M / F : 6 / 9 ) transplanted with unmanipulated BM from HLA identical sibling donors , persistently bcr / abl positive by RT PCR . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Expression of constitutively active Raf 1 in the mitochondria restores antiapoptotic and leukemogenic potential of a transformation deficient BCR / ABL mutant . ^^^ The oncogenic BCR / ABL protein protects hematopoietic cells from apoptosis induced by growth factor deprivation , but the mechanisms are only partially understood . ^^^ A BCR / ABL mutant lacking amino acids 176 426 in the BCR domain ( p185DeltaBCR ) failed to protect interleukin 3 deprived 32Dcl3 myeloid precursor cells from apoptosis , although it possessed tyrosine kinase activity and was capable of activating the Ras Raf MAP kinase pathway . ^^^ Moreover , constitutive expression of dominant negative M Raf ( K375W ) enhanced the susceptibility of 32Dcl3 cells expressing wild type BCR / ABL to apoptosis . ^^^ Together , these data support the existence of a BCR / ABL dependent pathway that leads to expression of an active RAF in the mitochondria and promotes antiapoptotic and leukemia inducing effects of BCR / ABL . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We have used interphase FISH ( fluorescence in situ hybridization ) and competitive RT PCR ( reverse transcriptase polymerase chain reaction ) techniques for detection of BCR ABL positive cells to measure suppression of leukaemic clone in a series of 51 follow up samples from 24 CML patients undergoing IFN alpha treatment . ^^^ Interphase FISH analysis of the malignant clone in bone marrow using BCR and ABL probes was found to be highly correlated to conventional G banding metaphase examination ( r = 0 . 98 ) . ^^^ RT PCR quantification of BCR ABL mRNA transcripts in blood also showed a high degree of concordance with the proportion of Ph positive metaphases ( r = 0 . 93 ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The ABL / BCR fusion gene on chromosome 9 in Ph negative chronic myelogenous leukemia : a case for vigilance in fluorescence in situ hybridization interpretation . ^^^ We report cytogenetic , fluorescence in situ hybridization ( FISH ) , and molecular analysis in a case of Ph negative chronic myelogenous leukemia patient with ABL / BCR fusion gene on chromosome 9 and a disparate FISH signal pattern using two commercially available bcr / abl probes ( Vysis , Inc . and Oncor , Inc . ) . ^^^ FISH studies using Vysis LSI bcr / abl probe in interphase cells demonstrated a BCR / ABL fusion pattern , similar to that of m BCR / ABL fusion found in acute lymphoblastic leukemia . ^^^ However , examination of metaphases revealed the ABL / BCR fusion signal on one of the chromosomes 9 , an ABL signal on the other chromosome 9 , and two BCR signals of different sizes on each of the chromosomes 22 . ^^^ Subsequently , a FISH study with the Oncor major ( M ) bcr / abl translocation probe confirmed the ABL / BCR fusion signal on chromosome 9 in addition to an ABL signal and a BCR signal located on chromosomes 9 and 22 , respectively . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
CTLs specific for bcr abl joining region segment peptides fail to lyse leukemia cells expressing p 210 bcr abl protein . ^^^ The aim of the current study was to determine whether immunization with synthetic peptides corresponding to the joining region segment of p 210 bcr abl chimeric protein can elicit CD8+ cytotoxic T lymphocytes ( CTLs ) capable of specifically lysing leukemia cells . ^^^ BALB / c mice were immunized with peptides identical to the joining region segment of p 210 bcr abl protein . ^^^ Class 1 major histocompatibility complex ( MHC ) restricted bcr abl peptide specific CD8+ CTLs were elicited . ^^^ The CTL clones were H 2 Kd restricted and specifically recognized a nonamer peptide of the combined sequence of bcr abl amino acids but neither bcr nor abl amino acid sequence alone . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The excessive proliferation of the myeloid marrow compartment in Philadelphia chromosome ( Ph ) positive acute and chronic leukemias has been largely attributed to a hyperactive and autonomously acting hybrid tyrosine kinase BCR ABL , a product of the fusion between the second exon of the c ABL proto oncogene and 5 ' portions of the BCR gene on chromosome 22 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Animals were killed at serial intervals ; cell suspensions and / or tissue sections from different organs were studied by immunohistochemistry and / or flow cytometry using antihuman CD 45 monoclonal antibodies ( MoAbs ) , and by fluorescence in situ hybridization ( FISH ) for the BCR ABL fusion gene . ^^^ FISH analysis with BCR and ABL probes showed that some of the human cells engrafting after injection of CP cells lacked a BCR ABL gene and were presumably normal . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Although the number of patients examined was small , these results indicate that the genes rearranged as a result of these chromosome translocations ( ABL , BCR , AML 1 and PML ) are not genomically imprinted . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We hypothesize that this fusion leads to constitutive activation of the FGFR 1 tyrosine kinase in a manner analogous to the activation of ABL by BCR in chronic myeloid leukemia . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The chromosomal abnormality in chronic myeloid leukemia ( CML ) results from a reciprocal translocation between chromosomes 9 and 22 transferring the c abl proto oncogene from chromosome 9 to the restricted breakpoint region on chromosome 22 M ( bcr ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
A two color BCR ABL probe that greatly reduces the false positive and false negative rates for fluorescence in situ hybridization in chronic myeloid leukemia . ^^^ The t ( 9 ; 22 ) translocation resulting in the fusion of BCR and ABL genes is pathognomonic in chronic myeloid leukemia ( CML ) and may be investigated at the molecular level using fluorescence in situ hybridization ( FISH ) . ^^^ Two color BCR ABL probes visualizing one fusion signal ( 1F FISH ) have high false positive rates ( FPR ) and false negative rates ( FNR ) . ^^^ The FPR is a result of the random spatial association of probe signals within normal interphase cells so that some cells appear to contain the BCR ABL fusion gene . ^^^ The FNR of 1F FISH probes depends on the distance between the BCR and ABL probes hybridized to the BCR ABL fusion gene ( < or =368 kb ) ; the `` gap ' ' between the signals causing the cell to be interpreted as normal . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Using a highly sensitive fluorescence in situ hybridization method with probes for BCR and ABL 1 ( D FISH ) , we studied 37 paired sets of bone marrow and blood specimens , collected within 24 to 96 hours of each other , from 10 patients before and during treatment for chronic myeloid leukemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
This chromosomal rearrangement leads to the fusion of the bcr and c abl genes and to the transcription of leukemia specific bcr abl mRNAs . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Although the TEL portion of the TEL / ABL fusion protein has no sequence similarity to that of BCR in the BCR / ABL protein , all forms of these fusion proteins contain a structure implicated in oligomerization . ^^^ Our results support the conclusion that the protein interaction domain of BCR and TEL , but not the Grb 2 binding site , are the important functional components in the activation of ABL kinase in haemopoietic discase . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
CD 4 ( + ) cytotoxic T cell clones specific for bcr abl b3a2 fusion peptide augment colony formation by chronic myelogenous leukemia cells in a b3a2 specific and HLA DR restricted manner . ^^^ In an attempt to elucidate the role of CD 4 ( + ) CTLs in immunosurveillance of chronic myelogenous leukemia ( CML ) , we examined the immunologic functions of bcr abl b3a2 fusion peptide specific CD 4 ( + ) CTL clones . ^^^ Seven CD 4 ( + ) T cell clones that responded to stimulation with b3a2 peptide , but not with b2a2 peptide or physiological counterparts bcr b3b4 and abl 1A a 2 peptides , were established from two healthy individuals . ^^^ These CD 4 ( + ) T cell clones exhibited b3a2 peptide specific and HLA DRB1 * 0901 restricted cytotoxicity and produced interleukin 3 ( IL 3 ) , IL 4 , IL 10 , interferon gamma , tumor necrosis factor alpha , and granulocyte macrophage colony stimulating factor in response to bcr abl peptide stimulation , indicating they were Th 0 clones . ^^^ These data suggest that bcr abl specific CD 4 ( + ) CTLs recognize CML cells in an antigen specific and HLA DR restricted manner , and that they do not inhibit , but in fact augment , CML cell growth . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The BCR / ABL junctional region and the b 3 exon from chronic myeloid leukaemia ( CML ) patients were sequenced . ^^^ In the eighth position before the junctional region of BCR / ABL cDNA , a cytosine replaces thymine in these cases . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
A Philadelphia negative chronic myeloid leukemia with a BCR / ABL fusion gene on chromosome 9 . ^^^ Fluorescence in situ hybridization with a BCR / ABL1 S probe , which is formatted to display a BCR / ABL fusion signal on chromosome 22 , gave a positive fusion signal on a chromosome 9 . ^^^ Therefore this patient has a BCR / ABL fusion gene on chromosome 9 . ^^^ These findings favor either a cryptic reciprocal exchange between BCR and ABL loci or the reversal of a Philadelphia translocation . ^^^ An insertion of BCR next to ABL is ruled out . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Alternatively , the fusion proteins BCR / ABL , ALL1 / AF 6 , EWS / ATF 1 , or NPM / ALK exhibit motifs for several common HLA specificities . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic myeloid leukemia ( CML ) is thought to arise from a pluripotent hematopoietic stem cell that has undergone a reciprocal translocation between the BCR gene on chromosome 22 and the ABL proto oncogene on chromosome 9 . ^^^ Moreover , evidence of BCR / ABL fusion was found in pluripotent stem cells ( CD 34 ( + ) Thy 1 ( + ) ) , B progenitor cells ( CD 34 ( + ) CD 19 ( + ) ) , T / NK progenitor cells ( CD 34 ( + ) CD 7 ( + ) cells ) , and T progenitor cells ( CD 34 ( + ) CD 7 ( + ) CD 5 ( + ) ) with a frequency equal to that in all CD 34 ( + ) cells isolated by FACS from bone marrow cells . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
A novel BCR ABL fusion gene ( e2 / 1a ) in a patient with Philadelphia positive chronic myelogenous leukaemia and an aggressive clinical course . ^^^ A novel variant BCR ABL mRNA transcript was detected by reverse transcription polymerase chain reaction ( RT PCR ) in a patient with Philadelphia positive ( Ph+ve ) chronic myelogenous leukaemia ( CML ) who had an aggressive clinical course . ^^^ Sequence analysis of the amplified cDNA fragment revealed an in frame fusion with part of BCR exon e 2 joined to part of ABL exon 1a . ^^^ This is the first report of breakpoints occurring within both ABL and BCR exons and the first fusion to involve ABL exon 1a . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The Ph chromosome is the result of a molecular rearrangement between the c ABL proto oncogene on chromosome 9 and the BCR ( breakpoint cluster region ) gene on chromosome 22 . ^^^ Most of ABL is linked with a truncated BCR . ^^^ The BCR / ABL fusion gene codes for an 8 kb mRNA and a novel 210 kDa protein which has higher and aberrant tyrosine kinase activity than the normal c ABL coded counterpart . ^^^ An etiological connection between BCR / ABL and leukemia is indicated by the observation that transgenic mice bearing a BCR / ABL DNA construct develop leukemia of B , T , and myeloid cell origin . ^^^ However , findings of our laboratory have shown that the BCR / ABL chimeric protein that is expressed in transfected cells may , under certain conditions , also increase the adhesion to fibronectin via enhanced expression of integrin . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
P 230 BCR / ABL protein may be associated with an acute leukaemia phenotype . ^^^ The BCR / ABL rearrangement , the molecular hallmark of chronic myelogenous leukaemia ( CML ) , is rare in acute myeloid leukaemia ( AML ) , being detected in approximately 1 % of cases . ^^^ Using reverse transcription polymerase chain reaction ( RT PCR ) we report a patient with an acute myeloid leukaemia phenotype at diagnosis who showed a BCR / ABL rearrangement with a breakpoint located in the micro bcr region ( e19a2 junction ) . ^^^ Immunoprecipitation and auto phosphorylation assay revealed the expression , by the patient ' s blast cells , of an abnormal P 230 BCR / ABL protein , which showed for the first time that this protein was constitutively activated in primary cells from patients . ^^^ This finding may contribute to the understanding of the role of the BCR / ABL rearrangements in determining different leukaemia phenotypes ranging from acute lymphoid and myeloid leukaemias to mild chronic neutrophilic leukaemias . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In conclusion , the results of this study indicate that a critical sequence in the human ber promoter may be used as a potential binding site for TFO designed to repress artificially the transcription of the fused bcr / abl gene expressed in leukemia cells . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Expression of BCR ABL in M 1 myeloid leukemia cells induces differentiation without arresting proliferation . ^^^ Because of its ability to mimic the proliferative and cell survival functions of hematopoietic growth factors , we hypothesized that the oncogene activated in CML , BCR ABL , might also influence differentiation . ^^^ To test this hypothesis , we examined the effects of expressing BCR ABL on the myeloid differentiation of murine M 1 leukemic cells , which cease dividing and differentiate into macrophages in the presence of the cytokines leukemia inhibitory factor ( LIF ) or interleukin ( IL ) 6 . ^^^ We found that BCR ABL induced macrophage differentiation in M 1 cells , accompanied by increased expression of macrophage cell surface markers and the acquisition of phagocytic ability . interestingly , clones of M 1 cells which expressed BCR ABL remained in cell cycle and were refractory to the growth inhibition and apoptosis induced by IL 6 or LIF in parental M 1 cells . ^^^ These data suggest that BCR ABL can stimulate both differentiation and proliferation and that these characteristics may contribute to the phenotype observed in CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The juxtaposition of ABL with BCR and risk for fusion may come at the time of BCR replication in late S phase . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Although chronic phase myelogenous leukaemia ( CML ) is characterised by the Philadelphia ( Ph ) chromosome leading to a fusion of the BCR and ABL genes , additional genetic alterations involved in blast crisis are poorly understood . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Selective induction of apoptosis in Philadelphia chromosome positive chronic myelogenous leukemia cells by an inhibitor of BCR ABL tyrosine kinase , CGP 57148 . ^^^ The BCR ABL tyrosine kinase has been implicated as the cause of Philadelphia chromosome ( Ph 1 ) positive leukemias . ^^^ We report herein that CGP 57148 , a selective inhibitor of the ABL tyrosine kinase , caused apoptosis specifically in bcr abl positive chronic myelogenous leukemia ( CML ) cells , K 562 and KYO 1 . ^^^ Upon treatment with CGP 57148 , CRKL , a specific substrate for BCR ABL that propagates signals via phosphatidylinositol 3 ' kinase ( PI3K ) , was dephosphorylated , indicating inhibition of BCR ABL tyrosine kinase at the cellular level . ^^^ These results indicate that CGP 57148 shows apoptogenic and anti proliferative effects on bcr abl positive cells by blocking BCR ABL initiated signaling pathways . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
A probe set for BCR and ABL verified breakpoints for all translocations involving chromosomes 9 and 22 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The P 190 , P 210 , and P 230 forms of the BCR / ABL oncogene induce a similar chronic myeloid leukemia like syndrome in mice but have different lymphoid leukemogenic activity . ^^^ The product of the Philadelphia chromosome ( Ph ) translocation , the BCR / ABL oncogene , exists in three principal forms ( P 190 , P 210 , and P 230 BCR / ABL ) that are found in distinct forms of Ph positive leukemia , suggesting the three proteins have different leukemogenic activity . ^^^ We have directly compared the tyrosine kinase activity , in vitro transformation properties , and in vivo leukemogenic activity of the P 190 , P 210 , and P 230 forms of BCR / ABL . ^^^ In a murine bone marrow transduction / transplantation model , the three forms of BCR / ABL were equally potent in the induction of a chronic myeloid leukemia ( CML ) like myeloproliferative syndrome in recipient mice when 5 fluorouracil ( 5 FU ) treated donors were used . ^^^ P 190 BCR / ABL induced lymphoid leukemia with shorter latency than P 210 or P 230 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Signal transducer and activator of transcription ( STAT ) 5 activation by BCR / ABL is dependent on intact Src homology ( SH ) 3 and SH 2 domains of BCR / ABL and is required for leukemogenesis . ^^^ We show here that BCR / ABL induces phosphorylation and activation of STAT 5 by a mechanism that requires the BCR / ABL Src homology ( SH ) 2 domain and the proline rich binding site of the SH 3 domain . ^^^ Upon expression in 32Dcl3 growth factor dependent myeloid precursor cells , STAT 5 activation deficient BCR / ABL SH3+SH2 domain mutants functioned as tyrosine kinase and activated Ras , but failed to protect from apoptosis induced by withdrawal of interleukin 3 and / or serum and did not induce leukemia in severe combined immunodeficiency mice . ^^^ In complementation assays , expression of a dominant active STAT5B mutant ( STAT5B DAM ) , but not wild type STAT5B ( STAT5B WT ) , in 32Dcl3 cells transfected with STAT 5 activation deficient BCR / ABL SH3+SH2 mutants restored protection from apoptosis , stimulated growth factor independent cell cycle progression , and rescued the leukemogenic potential in mice . ^^^ Moreover , expression of a dominant negative STAT5B mutant ( STAT5B DNM ) in 32Dcl3 cells transfected with wild type BCR / ABL inhibited apoptosis resistance , growth factor independent proliferation , and the leukemogenic potential of these cells . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Western blot analysis with specific antibodies to c Abl and Bcr proteins show that treatment of K 562 cells with a proteasome inhibitor results in significant reduction of Bcr Abl protein expression , which occurs several hours before the onset of apoptotic execution . ^^^ Levels of c Abl / p145 and Bcr / p160 proteins , however , remain essentially unaltered at that time . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Two patients with novel BCR / ABL fusion transcripts ( e8 / a2 and e13 / a2 ) resulting from translocation breakpoints within BCR exons . ^^^ We have identified novel BCR ABL mRNA fusions by RT PCR in two patients with Philadelphia ( Ph ) chromosome positive leukaemia . ^^^ Sequencing revealed in frame fusions consisting of part of BCR exon e 8 spliced to ABL exon a 2 in one patient and part of BCR exon e 13 spliced to ABL exon a 2 in the other . ^^^ These data show that BCR ABL translocation breakpoints can occasionally occur within coding exons . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BCR / ABL fusion proteins have a dysregulated protein tyrosine kinase ( PTK ) activity exerting a key role in malignant transformation . ^^^ Targeting the tyrosine kinase activity of BCR / ABL or using agents capable of triggering apoptosis might represent attractive therapeutic approaches for ex vivo purging . ^^^ AG 957 , a member of the tyrphostin compounds , exerts a selective inhibition of p 210 ( BCR / ABL ) tyrosine phosphorylation . ^^^ In 5 of 10 patients , analysis of BCR / ABL mRNA on single progenitors by reverse transcription polymerase chain reaction showed that AG 957 at 50 micromol / L significantly reduced the mean ( + / SD ) percentage of BCR / ABL positive progenitors ( 92 % + / 10 % 5 33 + / 5 % ; P = . 001 ) . ^^^ Because AG 957 treatment resulted in significantly higher percentages of apoptotic cells ( 30 % 5 9 % ) in the BCR / ABL transfected 32DLG7 cells as compared with 32D T2 / 93 cells ( BCR / ABL negative ) , we investigated the combined effects of AG 957 with the anti Fas receptor ( Fas R ) monoclonal antibody CH 11 that triggers apoptosis . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Mutator phenotype of BCR ABL transfected Ba / F3 cell lines and its association with enhanced expression of DNA polymerase beta . ^^^ Chronic myelogenous leukemia ( CML ) is characterized by the Philadelphia chromosome resulting from the translocation t ( 9 22 ) producing the chimeric 190 and 210 kDa BCR ABL fusion proteins . ^^^ Murine Ba / F3 cell line was transfected with the p 190 and p 210 encoding BCR ABL oncogenes , and spontaneous mutation frequency at the Na K ATPase and the hypoxanthine guanine phosphoribosyl transferase ( HPRT ) loci were measured . ^^^ Furthermore , we observed that BCR ABL transfection induced an overexpression of DNA polymerase beta , the most inaccurate of the mammalian DNA polymerases , as well as an increase in its activity , suggesting that inaccuracy of DNA replication may account for the observed mutator phenotype . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Tyrosine phosphorylation of Bcr by Fes greatly enhanced the binding of Bcr to the SH 2 domains of multiple signalling molecules in vitro , including Grb 2 , Ras GTPase activating protein , phospholipase C gamma , the 85 , 000 M ( r ) subunit of phosphatidylinositol 3 ' kinase , and the Abl tyrosine kinase . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Bcr : a negative regulator of the Bcr Abl oncoprotein . ^^^ Chronic myelogenous leukemia is typically characterized by the presence of the Philadelphia chromosome ( Ph ) in which 5 ' portions of the BCR gene are fused to a large portion of the ABL gene . ^^^ Our studies and those of others indicate that Bcr sequences within the Bcr Abl oncoprotein are critically involved in activating the Abl tyrosine kinase and actively participate in the oncogenic response , which is generated by the Bcr Abl oncoprotein . ^^^ We investigated the role of the Bcr protein in the oncogenic effects of Bcr Abl . ^^^ Reduction of the level of the Bcr protein by incubating cells with a 3 ' BCR anti sense oligodeoxynucleotide increased the growth rate and survival of hematopoietic cell lines expressing Bcr Abl . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The nuclear topography of ABL , BCR , PML , and RARalpha genes : evidence for gene proximity in specific phases of the cell cycle and stages of hematopoietic differentiation . ^^^ In this work , we have addressed this issue using as models the ABL and BCR genes of t ( 9 ; 22 ) and the PML and RARalpha genes of t ( 15 ; 17 ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
One of the ABL 1 promoters ( Pa ) and the coding region of the gene are usually translocated intact to the BCR locus , but the translocated promoter appears to be silent in most cases . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Bcr Abl with an SH 3 deletion retains the ability To induce a myeloproliferative disease in mice , yet c Abl activated by an SH 3 deletion induces only lymphoid malignancy . ^^^ The bcr abl oncogene plays a critical role in the pathogenesis of chronic myelogenous leukemia ( CML ) . ^^^ The fusion of Bcr sequences to Abl constitutively activates the Abl protein tyrosine kinase . ^^^ We have recently shown that expression of Bcr Abl in bone marrow cells by retroviral transduction efficiently induces in mice a myeloproliferative disease resembling human CML and that Abl kinase activity is essential for Bcr Abl to induce a CML like myeloproliferative disease . ^^^ In this study , we examined the role of the Abl SH 3 domain of Bcr Abl in induction of myeloproliferative disease and tested whether c Abl activated by SH 3 deletion can induce a CML like disease . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Atypical BCR and ABL D FISH patterns in chronic myeloid leukemia and their possible role in therapy . ^^^ Atypical patterns among Ph chromosomes were consistent with loss of the 3 ' portion of BCR that is usually translocated to chromosome 9 , or loss of the 5 ' segment of ABL that usually remains on chromosome 9 , or loss of both the 3 ' translocated BCR and 5 ' residual ABL hybridization sites . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
REN 26 is encoded by the bcr gene involved in the [ t ( 9 : 22 ) ] bcr / abl translocation . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Analysis of Philadelphia chromosome negative BCR ABL positive chronic myelogenous leukemia by hypermetaphase fluorescence in situ hybridization . ^^^ BACKGROUND : In 5 % 10 % of patients with of chronic myelogenous leukemia ( CML ) , the Philadelphia chromosome ( Ph ) is not identified , despite the presence of the associated BCR ABL molecular abnormality ( Ph negative , BCR ABL positive CML ) because of sub microscopic rearrangements . ^^^ PATIENTS AND METHODS : Six patients with Ph negative , BCR ABL positive CML were investigated . ^^^ The pattern of UBCR gene rearrangement was characterized by the same genomic recombination of 5 BCR and c ABL , both in the four cases of typical translocation ( 9 ; 22 ) and in the two cases of insertion of 9q34 into chromosome 22q11 . ^^^ CONCLUSIONS : The HMF identified two different bases for Ph negative , BCR ABL positive cells in CML presence of low frequency of cells with typical Ph translocations or presence of cells with ABL insertions into the BCR gene on chromosome 22 . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Insertion of the 5 ' part of BCR within the ABL gene at 9q34 in a Philadelphia negative chronic myeloid leukemia . ^^^ We report a chronic myeloid leukemia patient without evidence of a Philadelphia ( Ph ) chromosome in whom RT PCR analysis performed in blast crisis demonstrated the existence of both common b3a2 and b2a2 BCR / ABL fusion transcripts . ^^^ In situ hybridization studies with BCR and ABL specific probes showed location of the BCR / ABL fusion gene on chromosome 9 , band q 34 , instead of at chromosome 22q11 , and that it resulted from an insertion of the 5 ' side of BCR within the ABL gene on chromosome 9 . ^^^ The vast majority of cells showed a BCR / ABL fusion gene on both chromosomes 9 , which is equivalent to a double Ph chromosome , thus reinforcing the notion that the critical event in CML is the formation of a functional BCR / ABL fusion gene . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Thirteen chronic myeloid leukemia ( CML ) patients , 10 with variant Philadelphia ( Ph ) translocations and 3 Ph negative cases , were analyzed by fluorescence in situ hybridization ( FISH ) with the use of BCR and ABL cosmid probes and a chromosome 22 painting probe . ^^^ In the variant Ph translocations , the BCR ABL fusion gene was located on the Ph chromosome ; in 1 CML Ph negative patient , the BCR ABL fusion gene was located on the Ph chromosome ; and , in 2 patients , it was located on chromosome 9 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Fluorescence in situ hybridization ( FISH ) utilizing library probes , subtelomeric cosmid probes , and probes hybridizing to the ABL and BCR genes showed a reciprocal three way translocation involving Yq 12 , 9q34 , and 22q11 , and a BCR ABL fusion signal on der ( 22 ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Detection of BCR / ABL gene rearrangement and the elimination of rearranged clone in chronic myelocytic leukemia patients . ^^^ The RT PCR method was also applied to detect chimeric bcr / abl mRNA . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We sought to establish a rapid and reliable RT PCR approach for detection and quantification of BCR ABL fusion transcripts using the LightCycler technology . ^^^ A pair of probes was designed that was complementary to ABL exon 3 , thus enabling detection of all known BCR ABL variants and also normal ABL as an internal control . ^^^ To determine the utility of the assay , we quantified BCR ABL and ABL transcripts in 254 samples ( 222 peripheral blood , 32 bone marrow ) from 120 patients with CML after therapy with IFN alpha ( n = 219 ) , allogeneic BMT ( n = 17 ) , chemotherapy ( n = 11 ) , or at diagnosis ( n = 7 ) . ^^^ The level of residual disease in the 245 BCR ABL positive specimens was expressed as the ratio of BCR ABL / ABL . ^^^ A highly significant correlation was seen between the BCR ABL / ABL ratios determined by the LightCycler and ( 1 ) the BCR ABL / ABL ratios obtained by nested competitive RT PCR ( n = 201 , r = 0 . 90 , P < 0 . 0001 ) ; ( 2 ) the proportion of Philadelphia chromosome positive metaphases determined by cytogenetics ( n = 81 , P < 0 . 0001 ) ; and ( 3 ) the BCR ratio determined by Southern blot analysis ( n = 122 , P < 0 . 0001 ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Fluorescence in situ hybridization ( FISH ) studies confirmed the translocation and showed bcr / abl fusion on the der ( 22 ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
ABL BCR expression in BCR ABL positive human leukemia cell lines . ^^^ Expression of normal ABL and BCR and of reciprocal fusion genes BCR ABL and ABL BCR was examined in a panel of 53 BCR ABL positive cell lines by RT PCR to determine the influence of the various transcripts on leukemogenesis . ^^^ An ABL BCR transcript of the 1a splice variant was not detected in any of the cell lines . ^^^ Except for the lack of expression of normal BCR in m bcr cell lines and of ABL1a BCR expression in all cell lines , no consistent correlation of expression or lack of expression of BCR and ABL or of ABL BCR reciprocal fusion genes could be found with cell lineages and translocation types . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic myelogenous leukaemia with p 185 ( BCR / ABL ) expression : characteristics and clinical significance . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Complex chromosome rearrangements may locate the bcr / abl fusion gene sites other than 22q11 . ^^^ The BCR / ABL chimeric gene encoding for chimeric proteins is always present and maps on the 22q regardless of the type of translocation . ^^^ DESIGN AND METHODS : Dual color fluorescence in situ hybridization ( FISH ) can visualize BCR and ABL genes and localize the BCR / ABL fusion gene . ^^^ RESULTS : The chimeric BCR / ABL gene was located on a locus other than the expected 22q11 in both patients . ^^^ INTERPRETATION AND CONCLUSIONS : The location of the hybrid BCR / ABL gene on chromosomes other than 22q is a rare event which can only be observed using the FISH technique . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Alu and translisin recognition site sequences flanking translocation sites in a novel type of chimeric bcr abl transcript suggest a possible general mechanism for bcr abl breakpoints . ^^^ BACKGROUND AND OBJECTIVE : We further characterized a novel type of chimeric BCR ABL mRNA transcript detected in a patient with Philadelphia chromosome positive ( Ph+ ) chronic myeloid leukemia ( CML ) . ^^^ RESULTS : Part of exon e 8 of the BCR gene was joined to an intronic sequence of ABL intron Ib spliced on exon a 2 of the ABL gene , giving rise to an in frame e 8 int a 2 BCR ABL transcript . ^^^ The consequent BCR int ABL transcript was translated into a BCR ABL protein of 1804 amino acid residues with a molecular mass of 197 . 5 kilodaltons ( kDa ) called p 200 BCR ABL . ^^^ No differences in clinical or laboratory findings at diagnosis were found between this patient and CML patients with bcr abl fusion . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
DNA obtained from bone marrow cells at the time of lymphoma diagnosis showed BCR / ABL gene rearrangements by both Southern blot analysis and reverse transcription polymerase chain reaction ( RT PCR ) , but lacked both immunoglobulin and T cell receptor gene rearrangements . ^^^ BCR gene rearrangement and BCR / ABL fusion gene were also identified in lymph node and pleural biopsies by Southern blot and RT PCR analysis , respectively . ^^^ However , both biopsy specimens also contained reactive lymphocytes and neutrophils , and no fusion signals between BCR and ABL genes were identified in the hyperdiploid lymphoma cells of either case by fluorescence in situ hybridization ( FISH ) . ^^^ These data suggest the lymphoma cells in both cases were not genetically associated with BCR / ABL . ^^^ This represents the first definitive demonstration of peripheral B cell lymphoma occurring by a separate genetic pathway , lacking BCR / ABL , in patients with Ph ( + ) CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Complex chromosome 9 , 20 , and 22 rearrangements in acute lymphoblastic leukemia with duplication of BCR and ABL sequences . ^^^ FISH with the bcr / abl probe showed fusion of the BCR gene with the ABL gene ; however , this fusion signal was present in duplicate on both marker chromosomes . ^^^ To our knowledge , duplication of the BCR / ABL fusion signal on a single chromosome arm has not been reported before , except for the extensive amplification of BCR / ABL fusion signals in the leukemic cell line K 562 . ^^^ At the molecular level , the BCR / ABL fusion gene encodes the p 190 fusion protein . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
FISH , with the use of whole chromosome painting probes and probes specific for the BCR and ABL genes , showed a three way variant Philadelphia translocation ( 9 ; 22 ; 21 ) ( q 34 ; q 11 ; q 22 ) with a BCR / ABL fusion residing on the der ( 22 ) . ^^^ In addition , RT PCR demonstrated a b2a3 BCR / ABL fusion transcript . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In vivo inhibition by a site specific catalytic RNA subunit of RNase P designed against the BCR ABL oncogenic products : a novel approach for cancer treatment . ^^^ Using as a target model the abnormal BCR ABL p 190 and p 210 products , we constructed M 1 RNA with guide sequences that recognized the oncogenic messengers at the fusion point ( M 1 p190 GS and M 1 p210 GS ) . ^^^ To test the effectiveness and the specificity of M 1 p190 GS and M 1 p210 GS , we studied in vitro and in vivo effects of these RNA enzymes against BCR ABL ( p 190 ) and BCR ABL ( p 210 ) , bearing in mind that both fusion genes share the ABL sequence but differ in the sequence coming from the BCR gene . ^^^ We also demonstrated that when M 1 p190 GS and M 1 p210 GS were expressed in proper mammalian cell models , they abolished the effect of BCR ABL by specifically decreasing the amount of the target BCR ABL mRNA and preventing the function of the BCR ABL oncogenes . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In addition to this , chromosomes 9 and 22 were frequently associated in pairs detected as false positive ABL BCR fusions . ^^^ Similar topological characteristics of ABL and BCR genes were found in several cell lines : T and B lymphocytes . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The BCR ABL rearrangement was negative . ^^^ FISH analysis with the simultaneous and individual application of abl and bcr probes for chromosome 9 and 22 , respectively , revealed the presence of the BCR ABL rearrangement in addition to an extra ABL sequence locating chromosome 20 . ^^^ A clone that was BCR ABL gene rearrangement negative but with an extra ABL DNA sequence on chromsome 20 , and another clone that was BCR ABL gene rearrangement negative were detected by DC FISH and uni colour ( UC ) FISH analysis . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The influence of the cell cycle , differentiation and irradiation on the nuclear location of the abl , bcr and c myc genes in human leukemic cells . abl and bcr genes play an important role in the diagnostics of chronic myelogenous leukemia ( CML ) . ^^^ The chimeric bcr abl gene is a fundamental phenomenon in the pathogenesis of CML . ^^^ Nuclear topology of the abl , bcr and c myc genes was determined in differentiated as well as in irradiated HL 60 cells using dual colour fluorescence in situ hybridisation and image analysis by means of a high resolution cytometer . ^^^ After the induction of the granulocytic differentiation of HL 60 cells with all trans retinoic acid ( ATRA ) or dimethylsulfoxide ( DMSO ) , the abl and bcr homologous genes were repositioned closer to the nuclear periphery and the average distances between homologous abl abl and bcr bcr genes as well as between heterologous abl bcr genes were elongated as compared with untreated human leukemic promyelocytic HL 60 cells . ^^^ In the case of the monocytic maturation of HL 60 cells treated with phorbol esters ( PMA ) , the abl and bcr homologous genes were repositioned closer to each other and closer to the nuclear centre . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Seven cases did not have a BCR / ABL fusion signal . ^^^ The latest probe that is being used is the DBCR / ABL ( double reciprocal BCR / ABL signals ) . ^^^ The expected pattern for this probe is one green ABL signal ( 1G ) on the normal 9 , one red BCR signal ( 1R ) on the normal 22 , and two fusion signals , BCR / ABL and ABL / BCR ( 2F ) , on a derivative 22 and a derivative 9 , respectively . ^^^ The 1G1R1F pattern suggests that either the BCR and ABL breakpoints are different , or there are deletions at the breakpoints , because residual signals are not observed . ^^^ In one case of 2G1R1F , the plausible explanation is an insertion of ABL next to BCR and either a simultaneous or a sequential translocation with another chromosome . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The Philadelphia ( Ph ) chromosome , a characteristic cytogenetic marker of chronic myeloid leukaemia ( CML ) , is caused by a reciprocal translocation juxtaposing the 3 ' region of the ABL gene onto the 5 ' region of the BCR gene . ^^^ Due to conservation of the reading frame , but depending on the site of the breakpoint in the BCR gene , two alternatively spliced variants of the p210BCR ABL mRNA ( known as b 2 a2 and b 3 a2 ) are produced . ^^^ Morphological examination of the cells expressing either of the BCR ABL transcripts indicated that these cells were more mature with increased cytoplasm : nuclear ratios compared to the 32D parental and 32Dneo vector control cells . ^^^ At 10 ( 6 ) and 10 ( 7 ) cell doses all 32D cells expressing BCR ABL caused ill health and tissue infiltration in SCID mice with such rapidity that statistical analysis was not informative . ^^^ This panel of BCR ABL expressing 32D cells provides a useful model for CML disease progression studies . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Analysis of the biologic properties of p 230 Bcr Abl reveals unique and overlapping properties with the oncogenic p 185 and p 210 Bcr Abl tyrosine kinases . ^^^ The reciprocal translocation between chromosomes 9 and 22 that fuses coding sequences of the Bcr and Abl genes is responsible for a remarkably diverse group of hematologic malignancies . ^^^ A newly described 230 kd form of Bcr Abl has been associated with an indolent myeloproliferative syndrome referred to as chronic neutrophilic leukemia . ^^^ We have cloned the corresponding gene and examined the biologic and biochemical properties of p 230 Bcr Abl after retroviral mediated gene transfer into hematopoietic cell lines and primary bone marrow cells . p 230 Bcr Abl expressing 32D myeloid cells were fully growth factor independent and activated similar signal transduction pathways as the well characterized p 210 and p 185 forms of Bcr Abl . ^^^ The 3 Bcr Abl proteins exerted different effects on differentiation of bone marrow cells . p 185 induced outgrowth of lymphoid precursors capable of tumor formation in immunodeficient mice . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BCR ABL is a chimeric oncogene generated by translocation of sequences from the chromosomal counterpart ( c ABL gene ) on chromosome 9 into the BCR gene on chromosome 22 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Exon skipping in BCR / ABL is induced by ABL exon 2 . ^^^ The BCR / ABL fusion gene is pathognomonic for chronic myelogenous leukaemia ( CML ) . ^^^ We have previously reported alternative splicing of BCR / ABL , as indicated by the detection of both p 190 and p 210 encoding transcripts , in about 60 % of CML patient samples . ^^^ These exon skipping events involved the joining of ABL exon 2 to variable upstream BCR exons . ^^^ We have constructed BCR and BCR / ABL minigenes to study this phenomenon in more detail . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
An accelerrated phase CML patient with e19a2 junction of BCR / ABL gene the first case of transplanted CML with micro bcr . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
No data are available on their suitability for sensitive detection of breakpoint cluster region abelson ( BCR ABL ) gene transcripts . ^^^ In RNA samples extracted from lysed whole blood , the presence of amplifiable RNA / cDNA was confirmed by amplification of 4 selected reference genes ( porphobilinogen deaminase ( PBGD ) , ABL , the gene spanning the BCR on chromosome 22 and retinoic acid receptor alpha ( RARA ) ) in a multiplex PCR . ^^^ High quality , DNA free RNA was obtained with RNAzol , and 1 BCR ABL positive ( specific for translocation t [ 9 ; 221 ) cell among 2x10 ( 4 ) normal cells was successfully detectable by single step RT PCR . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
A small population of cells in acute lymphoblastic leukaemia is characterized by a specific translocation of the c abl oncogene on chromosome 9 to the break point cluster lesion ( bcr ) on chromosome 22 , t ( 9 ; 22 ) ( q 34 ; q 11 ) ( e1a2 ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BCR / ABL rearrangement in Philadelphia chromosome negative CML patients . ^^^ This report showed evidence of a chimeric BCR / ABL transcript in 18 ( 52 . 9 % ) and 28 ( 82 . 4 % ) cases by first PCR and seminested PCR , respectively . ^^^ In these BCR / ABL transcript positive cases , the incidence of BCR exon3 / ABL exon 2 ( B3A2 ) and BCR exon 2 / ABL exon 2 rearrangement was 25 ( 89 . 3 % ) and 3 ( 10 . 7 % ) cases , respectively . ^^^ This data demonstrates that seminested PCR is sufficiently sensitive to detect BCR / ABL fusion transcript in Ph chromosome negative CML patients . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
These include the idiotype proteins , breakpoint cluster region ( bcr ) abl and other fusion oncoproteins , myeloid specific differentiation antigens and minor histocompatibility antigens . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
A novel BCR ABL transcript ( e8a2 ) with the insertion of an inverted sequence of ABL intron 1b in a patient with Philadelphia positive chronic myeloid leukaemia . ^^^ An atypical BCR ABL transcript in a patient with Philadelphia ( Ph ) positive chronic myeloid leukaemia ( CML ) was detected using a long polymerase chain reaction technique . ^^^ Sequence analysis revealed a joining of BCR exon e 8 and ABL exon a 2 , with a 55 base pair ( bp ) insert of an inverted sequence of ABL intron 1b between them , giving rise to an in frame e8a2 BCR ABL transcript . ^^^ This is the first report of a BCR ABL transcript with the insertion of an inverted sequence . ^^^ The long PCR technique is a useful screen for atypical BCR ABL transcripts not detected by standard techniques . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The Grb 2 binding site is required for the induction of chronic myeloid leukemia like disease in mice by the Bcr / Abl tyrosine kinase . ^^^ The BCR / ABL oncogene results from a balanced translocation between chromosomes 9 and 22 and is found in patients with chronic myeloid leukemia ( CML ) and in some patients with acute B lymphoid leukemia . ^^^ The Bcr / Abl fusion protein is a constitutively active tyrosine kinase that stimulates several intracellular signaling pathways , including activation of Ras through direct binding of the SH 2 containing adapter protein Grb 2 to Bcr tyrosine 177 . ^^^ A tyrosine to phenylalanine mutation ( Y177F ) at this site blocks the co association of Bcr / Abl and Grb 2 in vivo and impairs focus formation by Bcr / Abl in fibroblasts . ^^^ However , the Bcr / Abl Y177F mutant can transform hematopoietic cell lines and primary bone marrow cells in vitro , so the importance of the Bcr / Abl Grb 2 interaction to myeloid and lymphoid leukemogenesis in vivo is unclear . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic myelogeneous leukaemia ( CML ) is genetically characterized by the fusion of parts of the BCR and ABL genes on chromosomes 22 and 9 , respectively . ^^^ SPDM was applied to analyse the 3D chromatin structure of the BCR region on the intact chromosome 22 and the BCR ABL fusion gene on the Philadelphia chromosome ( Ph ) by using a new triple colour FISH protocol : two different DNA probes were used to detect the BCR region and the third DNA probe was used to identify the location of the ABL gene . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Detailed mapping of methylcytosine positions at the CpG island surrounding the Pa promoter at the bcr abl locus in CML patients and in two cell lines , K 562 and BV 173 . ^^^ Chronic myelogenous leukemia ( CML ) is associated with a translocation of the protooncogene c abl from chromosome 9 to chromosome 22 , where it fuses to proximal exons of the bcr gene . ^^^ The expression of the hybrid gene bcr abl is regulated by the bcr promoter and results in a translation product with high tyrosine kinase activity . ^^^ In most CML cases , one of two abl promoters ( Pa ) is nested within the bcr abl transcription unit , but appears to be usually silent . ^^^ Variant methylation observed in K 562 cells correlates with multiple bcr abl loci and an intact chromosome 9 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Autoantibodies to Abl and Bcr proteins . ^^^ Formation of an aberrant , chimeric Bcr Abl protein is the hallmark of Philadelphia ( Ph ) chromosome positive leukemias . ^^^ The Bcr Abl protein , as well as its normal cellular counterparts Abl and Bcr are intracellular molecules with postulated roles in a variety of critical biologic functions . ^^^ In all 18 patients , plasma was able to recognize baculovirus expressed Abl protein ; in four patients , recognition of baculovirus expressed Bcr protein was also demonstrated . ^^^ These observations suggest that a humoral immune response to p210Bcr Abl is discernible in both Ph positive and negative leukemias and in healthy individuals , and is most likely due to autoantibodies which recognize normal Abl and , to a lesser extent , normal Bcr proteins . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
FISH with BCR / ABL probes showed that 39 % and 57 % of interphase nuclei had double and triple BCR / ABL fusion signals , respectively . ^^^ Rearrangement of major breakpoint cluster region ( M bcr ) in the BCR gene and coexpression of p 210 type ( b2a2 ) and p 190 type ( e1a2 ) BCR / ABL fusion transcripts due to alternative splicing were also detected . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Regarding t ( 9 ; 22 ) , the breakpoint on chromosome 22 occurred in the mu BCR region of the BCR gene , resulting in hybrid BCR / ABL mRNA with an e19a2 junction . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Repeated analyses for the Philadelphia chromosome ( Ph 1 ) , rearrangement of the BCR gene or chimeric BCR / ABL mRNA , major , minor and mu , were negative . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Frequent polymorphism in BCR exon b 2 identified in BCR ABL positive and negative individuals using fluorescent hybridization probes . ^^^ Recently , a polymorphic base in exon 13 of the BCR gene ( exon b 2 of the major breakpoint cluster region ) has been identified in the eighth position before the junctional region of BCR ABL cDNA . ^^^ Therefore , this polymorphism has no implication in the primary structure of BCR and BCR ABL proteins . ^^^ We have developed a RT PCR based screening method to easily identify polymorphic BCR and BCR ABL alleles in CML patients and normal individuals in order to estimate their frequency . ^^^ After amplification from cDNA , a melting curve of a specific fluorogenic probe mapping to the 3 ' end of BCR exon b 2 and spanning the polymorphism readily discriminates between normal and polymorphic BCR and BCR ABL alleles . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Bcl 2 expression restores the leukemogenic potential of a BCR / ABL mutant defective in transformation . ^^^ Growth factor dependent hematopoietic cell lines expressing the BCR / ABL oncoprotein of the Ph chromosome show growth factor independent proliferation and resistance to apoptosis . ^^^ Apoptosis resistance of BCR / ABL expressing cells may depend on enhanced expression of anti apoptotic proteins as well as reduced expression and / or inactivation of pro apoptotic proteins . ^^^ Compared to myeloid precursor 32Dcl3 cells expressing wild type BCR / ABL , cells expressing a BCR / ABL mutant lacking amino acids 176 426 in the BCR domain ( p 185 delta BCR ) are susceptible to apoptosis induced by interleukin 3 ( IL 3 ) deprivation . ^^^ Upon ectopic expression of Bcl 2 , these cells showed no changes in BAD phosphorylation , but they became apoptosis resistant and proliferated in the absence of IL 3 , albeit more slowly than cells expressing wild type BCR / ABL . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The model consists of a linear quadratic dose response for the induction of BCR ABL , a waiting time distribution between BCR ABL formation and detection of CML , and an exponential cell killing term that multiplies both the background and induced incidence rates . ^^^ S . population , and genomic DNA target sizes of BCR and ABL . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
A three zinc finger protein that binds specifically to the cDNA representing the unique fusion gene BCR : Abl , associated with acute lymphoblastic leukaemia , has previously been characterised . ^^^ At this breakpoint , a sequence homology of 8 / 9 bp exists between the BCR : Abl ( fusion ) and c ABL : ( parental ) target sequences . ^^^ We show that the three zinc finger protein discriminates poorly between the fusion ( BCR : Abl ) and parental ( ABL : ) sequence ( K : ( d ) s of 42 . 8 and 65 . 1 nM , respectively ) . ^^^ This fourth finger recognises a 3 bp subsite derived from the BCR : portion of the breakpoint and is not present in c ABL : This novel four finger protein , which now recognises a 12 bp sequence , demonstrates improved specific binding to BcrAbl ( K : ( d ) = 17 nM ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Novel type of BCR ABL transcript in a chronic myelogenous leukaemia patient relapsed after bone marrow transplantation . ^^^ We identified a novel BCR ABL transcript in a chronic myelogenous leukaemia ( CML ) patient who relapsed after bone marrow transplantation ( BMT ) , containing a fusion between part of BCR exon 3 , 44 nucleotides derived from ABL intron 1b and ABL exon 2 . ^^^ The breakpoints were located within BCR exon 3 on chromosome 22 and within the ABL intron 1b on chromosome 9 , and the transcript derives from a splicing of ABL exon 2 to a putative splicing acceptor site 44 nucleotides downstream to the breakpoint on chromosome 9 . ^^^ The patient ' s clinical course strengthens the idea that short forms of BCR ABL transcripts are associated with a more aggressive disease . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The NH ( 2 ) terminal coiled coil domain and tyrosine 177 play important roles in induction of a myeloproliferative disease in mice by Bcr Abl . ^^^ Bcr Abl , a fusion protein generated by t ( 9 ; 22 ) ( q 34 ; q 11 ) translocation , plays a critical role in the pathogenesis of chronic myelogenous leukemia ( CML ) . ^^^ It has been shown that Bcr Abl contains multiple functional domains and motifs and can disrupt regulation of many signaling pathways and cellular functions . ^^^ However , the role of specific domains and motifs of Bcr Abl or of specific signaling pathways in the complex in vivo pathogenesis of CML is not completely known . ^^^ We have previously shown that expression of Bcr Abl in bone marrow cells by retroviral transduction efficiently induces a myeloproliferative disorder ( MPD ) in mice resembling human CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
PBPC mobilization with chemotherapy and G CSF in patients with chronic myeloid leukemia : quantification of bcr / abl positive cells by interphase fluorescence in situ hybridization and competitive PCR . ^^^ Thus , quantification of possible contamination of progenitor cell apheresis with breakpoint cluster region ( bcr ) / Abelson murine leukemia ( abl ) positive cells is of great clinical interest . ^^^ STUDY DESIGN AND METHODS : Two molecular methods were compared to quantify bcr / abl positivity in leukapheresis components obtained after mobilizing chemotherapy in six patients with CML . ^^^ To document the efficacy of in vivo purging , the leukapheresis procedures were monitored with interphase fluorescence in situ hybridization ( FISH ) and quantitative competitive PCR ( QC PCR ) as a ratio of bcr / abl : abl . ^^^ RESULTS : From the first to the last leukapheresis , bcr / abl positivity in FISH increased from a median of 11 percent to 33 percent . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Are aberrant BCR ABL transcripts more common than previously thought . ^^^ We report the use of multiplex polymerase chain reaction ( PCR ) , using 4 % polyacrylamide gel electrophoresis ( PAGE ) for the detection of BCR ABL transcripts in Philadelphia positive disease . ^^^ We suggest that multiplex PCR using 4 % PAGE and optimized for smaller transcript detection may lead to a higher detection rate of rare BCR ABL breakpoints . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Imaging properties of fluorescent beads of three different diameters ( 0 . 1 microm , 0 . 2 microm , and 0 . 5 microm ) as well as imaging properties of four different fluorescence stained DNA targets ( ABL gene , BCR gene , centromere 6 , and centromere 17 ) are studied . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Activation of c Abl kinase activity and transformation by a chemical inducer of dimerization . c Abl is a non receptor tyrosine kinase that is activated in human leukemias by the fusion of Bcr or Tel sequences to the Abl NH ( 2 ) terminus . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Glucose transport regulation by p 210 Bcr Abl in a chronic myeloid leukaemia model . ^^^ In this study , we found that activation of Bcr Abl protein tyrosine kinase was associated with the stimulation of glucose transport in the multipotent haemopoietic cell line FDCP mix , a cell model for chronic phase chronic myeloid leukaemia ( CML ) . ^^^ Bcr Abl upregulation of glucose transport was mediated by phosphatidylinositol 3 kinase . ^^^ The observation that Bcr Abl can regulate glucose transport in a CML cell model raises the possibility that glucose transport regulation may have a role to play in the aberrant survival of stem cells in the chronic phase of CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The 2 phenylaminopyrimidine derivative STI 571 has been shown to selectively inhibit the tyrosine kinase domain of the oncogenic bcr / abl fusion protein . ^^^ The activity of this inhibitor has been demonstrated so far both in vitro with bcr / abl expressing cells derived from leukemic patients , and in vivo on nude mice inoculated with bcr / abl positive cells . ^^^ Yet , no information is available on whether leukemic cells can develop resistance to bcr / abl inhibition . ^^^ The human bcr / abl expressing cell line LAMA 84 was cultured with increasing concentrations of STI 571 . ^^^ LAMA84R cells showed increased levels of bcr / abl protein and mRNA when compared to LAMA 84 cells . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Treatment of Bcr / Abl positive acute lymphoblastic leukemia in P 190 transgenic mice with the farnesyl transferase inhibitor SCH 66336 . ^^^ The Ph translocation joins the BCR and ABL genes and leads to expression of a chimeric Bcr / Abl protein with enhanced tyrosine kinase activity . ^^^ One important pathway activated by Bcr / Abl is the Ras pathway . ^^^ We studied the effect of the farnesyl transferase inhibitor SCH 66336 in an in vivo murine model of Bcr / Abl positive acute lymphoblastic leukemia . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We demonstrate that suitable masked antisense RNA can discriminate between the two forms of BCR ABL mRNA that result from the Philadelphia chromosomal translocations , as well as discriminating the normal BCR and ABL mRNA . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We aimed to analyze DNA of chronic phase and blastic phase archive material of 15 CML patients for LOH using D1S430 , D2S123 , D3S1611 , D11S29 , D14S65 , D17S520 , BAT 40 markers , the dinucleotide repeat located in the ABL gene and the trinucleotide repeat located in the BCR gene ( amplification of the trinucleotide in the BCR gene could not be succeeded ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Reverse transcription polymerase chain reaction showed the major and minor bcr / abl fusion transcripts in the cells from a bone marrow ( BM ) sample . ^^^ Fluorescence in situ hybridization ( FISH ) analysis also showed that fusion signals of the bcr and abl probes were found in 95 % of blastic cells and in 64 % of neutrophils . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Mechanisms of transformation by the BCR / ABL oncogene . ^^^ The Philadelphia chromosome generates a chimeric oncogene in which the BCR and c ABL genes are fused . ^^^ The product of this oncogene , BCR / ABL , has elevated ABL tyrosine kinase activity , relocates to the cytoskeleton , and phosphorylates multiple cellular substrates . ^^^ BCR / ABL transforms hematopoietic cells and exerts a wide variety of biological effects , including reduction in growth factor dependence , enhanced viability , and altered adhesion of chronic myelocytic leukemia ( CML ) cells . ^^^ Elevated tyrosine kinase activity of BCR / ABL is critical for activating downstream signal transduction and for all aspects of transformation . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Pathological generation of BCR ABL ( breakpoint cluster region Abelson ) results in growth promotion , differentiation , resistance to apoptosis , and defect in DNA repair in targeted blood cells . ^^^ Domains in BCR and ABL sequences work in concert to elicit a variety of leukemogenic signals including Ras , STAT 5 ( signal transducer and activator of transcription 5 ) , Myc , cyclin D 1 , P 13 ( phosphatidylinositol 3 kinase ) , RIN 1 ( Ras interaction / interference ) , and activation of actin cytoskeleton . ^^^ A mutator phenotype of BCR ABL could explain the transformation to blast crisis . ^^^ The aim of this review is to integrate molecular and biological information on BCR , ABL , and BCR ABL and to focus on how signaling from those molecules mirrors the biological phenotypes of chronic myeloid leukemia . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Inferences from BCR and ABL geometric distributions . ^^^ CML is known to be caused by a translocation involving the ABL and BCR genes , almost all CML patients have the BCR ABL translocation , and CML is prevalent enough that its induction is unequivocally detected among Hiroshima A bomb survivors . ^^^ This estimate assumed that BCR ABL translocation dose response curves in stem cells for both neutrons and gamma rays , differ only by a common proportionality constant from dicentric aberration dose response curves in lymphocytes . ^^^ In the present paper we challenge this assumption by predicting the BCR ABL dose response . ^^^ The predictions are based on the biophysical theory of dual radiation action ( TDRA ) as it applies to recent BCR to ABL distance data in G 0 human lymphocytes ; this data shows BCR and ABL geometric distributions that are not uniform and not independent , with close association of the two genes in some cells . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Aberrant BCR ABL transcript with intronic insertion in a patient with philadelphia chromosome positive chronic myeloid leukemia : implications for disease progression . ^^^ The BCR ABL fusion gene is important for the leukemogenesis of chronic myeloid leukemia ( CML ) . ^^^ A relationship between types of BCR ABL transcripts in CML and clinical features has been proposed . ^^^ We present here a patient with CML who carried an aberrant BCR ABL transcript with an intronic sequence insert . ^^^ Reverse transcription polymerase chain reaction detected an atypically large BCR ABL mRNA transcript . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Time course of chimerism and minimum residual illness was studied by standard cytogenetic methods , fluorescent in situ hybridization ( FISH ) with DNA probes to centromer sites of 10 and Y chromosomes and BCR and ABL genes . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
A variant form of myelodysplastic syndrome with Ph minor BCR / ABL transcript . ^^^ This study concerns a patient with minor ( m ) BCR / ABL transcript positive and Philadelphia ( Ph ) chromosome negative myelodysplastic syndrome ( MDS ) . ^^^ Molecular genetic studies , using reverse transcriptase polymerase chain reaction analysis detected m BCR / ABL messenger RNA . ^^^ Fluorescence in situ hybridization , however , revealed fusion signals of BCR and ABL probes on an apparently normal chromosome 22 . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Nonrandom distribution of interspersed repeat elements in the BCR and ABL 1 genes and its relation to breakpoint cluster regions . ^^^ The Philadelphia translocation , t ( 9 ; 22 ) ( q 34 ; q 11 ) , is the microscopically visible product of recombination between two genes , ABL 1 on chromosome 9 and BCR on chromosome 22 , and gives rise to a functional hybrid BCR ABL 1 gene with demonstrated leukemogenic properties . ^^^ The mechanisms that determine preferential breakage sites in BCR , and which cause recombination between BCR and ABL 1 , are presently unknown . ^^^ For the present study , we carried out a detailed analysis of genomic BCR and ABL 1 sequences to identify , classify , and locate interspersed repeat sequences and to relate their distribution to precisely mapped BCR ABL 1 recombination sites . ^^^ A significant lack of Alu elements was observed across the major and minor breakpoint cluster regions of BCR and across a 25 kb region showing a high frequency of breakage in ABL 1 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BACKGROUND : The human Bcr gene was originally identified by its presence in the chimeric Bcr / Abl oncogene , which is causative for chronic myeloblastic leukemia . ^^^ Because phosphatidylinositol 3 ' kinase ( PI 3 K ) is essential for Bcr / Abl leukemogenesis , we evaluated the role of mouse PDGF beta receptor binding sites for PI 3 K ( Y 708 , Y 719 ) and for phospholipase C gamma ( Y 977 , Y 989 ) in PDGF mediated Bcr kinase activation . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Phosphatidyl inositol signaling by BCR / ABL : opportunities for drug development . ^^^ The t ( 9 ; 22 ) translocation associated with chronic myelogenous leukemia ( CML ) fuses the c ABL gene on chromosome 9 with the BCR gene on chromosome 22 , resulting in the production of one or more of a family of chimeric oncoproteins , p 190 , p 210 , or p 230 BCR / ABL . ^^^ Recent studies have led to the identification of numerous potential substrates for BCR / ABL , including many proteins that normally function in signal transduction pathways downstream from hematopoietic growth factor receptors . ^^^ BCR / ABL is autophosphorylated on tyrosine residues and attracts a variety of adapter proteins and other signaling proteins , setting up large signaling complexes that ultimately result in growth . viability , and adhesion signals . ^^^ Furthermore , the relative importance of some BCR / ABL activated pathways is becoming clear . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The t ( 9 ; 22 ) ( q 34 ; q 11 ) produces the BCR / ABL fusion gene which codifies a 210 kb protein with a strong tyrosine kinase activity and is involved in cellular development and growth . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BCR ABL , ABL BCR , BCR , and ABL genes are all expressed in individual granulocyte macrophage colony forming unit colonies derived from blood of patients with chronic myeloid leukemia . ^^^ It has been suggested that the BCR ABL gene of chronic myeloid leukemia ( CML ) is not uniformly expressed in Philadelphia ( Ph ) positive cells , and that BCR ABL gene expression precludes transcription of the normal BCR or ABL genes . ^^^ Therefore , we have analyzed granulocyte macrophage colony forming unit ( CFU GM ) colonies derived from peripheral blood of 11 CML patients by cytogenetic and by reverse transcriptase polymerase chain reaction ( PCR ) amplification of BCR ABL , ABL BCR , BCR , and ABL . ^^^ In 2 patients , the initial PCR screening failed to detect BCR ABL transcripts in 2 of 11 and 1 of 7 Ph positive colonies . ^^^ However , when amplification for BCR ABL was repeated in quintuplicate , all but 1 colony from a single patient showed one or more positive results . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Fusion of the BCR and the fibroblast growth factor receptor 1 ( FGFR 1 ) genes as a result of t ( 8 ; 22 ) ( p 11 ; q 11 ) in a myeloproliferative disorder : the first fusion gene involving BCR but not ABL . ^^^ In this respect , the t ( 9 ; 22 ) ( q 34 ; q 11 ) that results in the BCR / ABL fusion gene in chronic myeloid leukemia is one of the best studied examples . ^^^ By analogy with data obtained from previously characterized fusion genes involving FGFR 1 and BCR / ABL , it is likely that the oligomerization domain contributed by BCR is critical and that its dimerizing properties lead to aberrant FGFR 1 signaling and neoplastic transformation . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The FISH studies on CML marrows in complete cytogenetic remission ( CCR ) ( 100 % Ph by CK ) achieved by IFN alpha , showed 0 2 . 5 % of cells with BCR ABL fusion in first cytogenetic remission ( Controls , range 0 . 5 1 . 5 % ) . ^^^ Repeat follow up FISH studies could be done in two cases in remission , which demonstrated 0 10 % of cells with BCR ABL fusion . ^^^ Evaluation of Ph positive status of CML marrow at diagnosis by CK ( 100 % Ph+ cells ) and FISH ( 80 92 % BCR ABL fusion ) pointed the existence of dormant clone of normal residual hematopoietic cells along with actively proliferating clones of Ph positive cells . ^^^ Among 14 patients , 9 who showed percentage of BCR ABL positive cells ( 0 . 0 1 . 5 % ) almost similar to normal controls , 6 patients had comparatively good prognosis ( disease free survival 7 14 months ) . ^^^ In the present studies , FISH on interphase cells also demonstrated its efficiency in the molecular diagnosis by its ability to detect BCR ABL and PML RARA fusion in CML with masked / variant Ph and t ( 15 ; 17 ) negative APL , respectively . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Bcr gene was originally identified by its presence in the chimeric Bcr / Abl oncogene . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Inhibition of the Bcr Abl oncoprotein by Bcr requires phosphoserine 354 . ^^^ The BCR protein is involved in the inhibition of oncogenic activity of the Bcr Abl oncoprotein . ^^^ This inhibition is believed to be the result of binding to the SH 2 domain of Bcr Abl in a non phosphotyrosine dependent manner . ^^^ We showed that the Arg to Leu mutation in the Phe Leu Val Arg Glu Ser ( FLVRES ) sequence of the SH 2 domain , known to interfere with phosphotyrosine sequence binding , did not block the binding of Bcr first exon sequences to the Abl SH 2 domain . ^^^ Abl SH 2 binding experiments indicated that the M ( r ) 55 , 000 species of Bcr ( 64 413 ) but not the M ( r ) 45 , 000 47 , 000 species bound strongly to glutathime transferase Abl SH 2 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Intracellular antibody capture technology : application to selection of intracellular antibodies recognising the BCR ABL oncogenic protein . ^^^ Accordingly , we have isolated panels of scFv that bind intracellularly to the BCR or the ABL parts of the BCR ABL oncogenic protein . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Heterogenic molecular basis for loss of ABL 1 BCR transcription : deletions in der ( 9 ) t ( 9 ; 22 ) and variants of standard t ( 9 ; 22 ) in BCR ABL 1 positive chronic myeloid leukemia . ^^^ The objective of this study was to characterize the ABL 1 BCR fusion gene in 76 BCR ABL 1 positive chronic myeloid leukemia ( CML ) patients regarding expression as well as genomic status , to assess the frequency of ABL 1 BCR gene deletion in these patients , which has been reported to be an adverse prognostic factor in Philadelphia chromosome positive CML . ^^^ Patients were analyzed for ABL 1 BCR 1b b 3 and / or 1b b 4 transcription by RT PCR analysis . ^^^ ABL 1 BCR gene status was analyzed by FISH in 16 CML patients with no ABL 1 BCR transcript . ^^^ FISH revealed a partial or total deletion of the ABL 1 BCR gene in 9 / 16 and localized the 5 ' portion of ABL 1 and the 3 ' portion of BCR at separated loci in 5 / 16 patients . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Relationship of the BCR gene breakpoint and the type of BCR / ABL transcript to clinical course , prognostic indexes and survival in patients with chronic myeloid leukemia . ^^^ At the molecular level a fusion of part of the ABL and BCR genes is observed . ^^^ In 61 patients the type of BCR / ABL transcript was determined , and in 27 patients BCR breakpoints were established . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Several patients with clinical features of chronic myeloid leukemia ( CML ) have fusion of the TEL ( ETV 6 ) gene on 12p13 with ABL on 9q34 and express a chimeric Tel Abl protein that contains the same portion of the Abl tyrosine kinase fused to Tel , an Ets family transcription factor , rather than Bcr . ^^^ In a murine retroviral bone marrow transduction transplantation model , a Tel ( exon 1 5 ) Abl fusion protein induced 2 distinct illnesses : a CML like myeloproliferative disease very similar to that induced by Bcr Abl but with increased latency and a novel syndrome characterized by small bowel myeloid cell infiltration and necrosis , increased circulating endotoxin and tumor necrosis factor alpha levels , and fulminant hepatic and renal failure . ^^^ CML like disease induced by Tel Abl and Bcr Abl was polyclonal and originated from cells with multilineage ( myeloid , erythroid , and B and T lymphoid ) repopulating ability and the capacity to generate day 12 spleen colonies in secondary transplantations . ^^^ In contrast to findings with Bcr Abl , however , neither Tel Abl induced disease could be adoptively transferred to irradiated secondary recipient syngeneic mice . ^^^ These results show that Tel Abl has leukemogenic properties from distinct from those of Bcr Abl and may act in a different bone marrow progenitor . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BCR / ABL p 210 , p 190 and p 230 fusion genes in 250 Mexican patients with chronic myeloid leukaemia ( CML ) . ^^^ There are two major forms of the BCR / ABL fusion gene , involving ABL exon 2 , but including different exons of BCR gene . ^^^ We performed nested and multiplex reverse transcriptase polymerase chain reaction ( RT PCR ) on bone marrow samples from adult patients and found that all cases were positive for some type of BCR / ABL rearrangement . ^^^ Our study confirms the occurrence of coexpression of different BCR / ABL transcripts , although the rate ( 9 . 6 % ) was much lower than has been reported in other populations . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Detection of bcr / abl gene expression on bone marrow cell colonies in chronic myelogenous leukemia by reverse transcriptase polymerase chain reaction ] . ^^^ The t ( 9 ; 22 ) ( q 34 ; q 11 ) between abl and bcr genes plays a pivotal role in the diagnosis and pathogenesis of chronic myelogenous leukemia ( CML ) . ^^^ To explore the bcr / abl fusion mRNA expression on hematopoietic precursors , reverse transcriptase polymerase chain reaction ( RT PCR ) was applied to detect bcr / abl mRNA expression on bone marrow cell colonies . ^^^ Meanwhile , bcr / abl mRNA expressions on 14 or 28 day colonies using HPP CFC and CFU GM semisolid agar culture assay were also determined in 4 cases of confirmed Ph positive CML by karyotyping analysis . ^^^ The results showed that the bcr / abl mRNA expressions on 14 day colonies and some 14 or 28 day colonies detected singly were positive at presentation by RT PCR , in agreement with results by karyotype analysis . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Novel types of bcr abl transcript with breakpoints in BCR exon 8 found in Philadelphia positive patients with typical chronic myeloid leukemia retain the sequence encoding for the DBL and CDC 24 homology domains but not the pleckstrin homology one . ^^^ BACKGROUND AND OBJECTIVES : We previously described a novel type of the chimeric bcr abl mRNA transcript in a patient with a Philadelphia chromosome positive chronic myeloid leukemia . ^^^ A similar bcr abl transcript has also been described by others . ^^^ DESIGN AND METHODS : Sequence analysis of the fusion region showed a join between part of exon e 8 of the bcr gene and an intronic sequence of abl intron 1b spliced on exon a 2 of the abl gene , giving rise to an in frame e 8 int a 2 bcr abl transcript , translated into a 197 . 5 kDa BCR ABL protein of 1804 amino acid residues , which we named p 200 BCR ABL . ^^^ RESULTS : In this work , employing protein comparison analysis ( pFAM ) we show that these novel bcr abl transcripts retain the DBL homology ( DH ) domain and the recently recognized CDC 24 homology domain , but not the pleckstrin homology ( PH ) domain of the bcr gene . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In the 1980s , the molecular counterpart of the chromosomal rearrangement was identified to consist of the juxtaposition of parts of the BCR and ABL genes to form a BCR ABL hybrid gene . ^^^ Although many aspects of the BCR ABL driven transformation remain unsolved , great advances in understanding the molecular pathology of Ph positive leukemias resulted in meaningful improvement in the clinical setting . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
A 76 kb duplicon maps close to the BCR gene on chromosome 22 and the ABL gene on chromosome 9 : possible involvement in the genesis of the Philadelphia chromosome translocation . ^^^ A patient with a typical form of chronic myeloid leukemia was found to carry a large deletion on the derivative chromosome 9q+ and an unusual BCR ABL transcript characterized by the insertion , between BCR exon 14 and ABL exon 2 , of 126 bp derived from a region located on chromosome 9 , 1 . 4 Mb 5 ' to ABL . ^^^ The discovery of a large duplicon relatively close to the ABL and BCR genes and the finding that the 126 bp insertion is very close to the duplicon at 9q34 open the question of the possible involvement of the duplicon in the formation of the Philadelphia chromosome translocation . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The inadvertent fusion of the bcr gene with the abl gene results in a constitutively active tyrosine kinase ( Bcr Abl ) that transforms cells and causes chronic myelogenous leukemia . ^^^ Small molecule inhibitors of Bcr Abl that bind to the kinase domain can be used to treat chronic myelogenous leukemia . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We used probes for the short arm of chromosome 12 , for ABL 1 and BCR , for centromeric regions , and for whole chromosome arms . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Bcr Abl is an oncogene that arises from fusion of the Bcr gene with the c Abl proto oncogene . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BACKGROUND : Chronic myeloid leukaemia ( CML ) is a haematopoietic malignancy characterized by the presence of the Philadelphia ( Ph ) chromosome that results from balanced reciprocal translocation between chromosomes 9 and 22 leading to the formation of the bcr / abl fusion gene . ^^^ Studies have shown that interferon alpha ( IFN alpha ) therapy induces both cytogenetic ( reduction in Ph+ cells ) and molecular response ( reduction in the bcr / abl positive cells ) in a large proportion of patients , thereby improving their prognosis and survival . ^^^ Dual colour fluorescence in situ hybridization ( FISH ) analysis using specific probes for bcr and abl genes was done to assess the molecular response . ^^^ Using FISH analysis , 4 of these patients were negative for the fusion gene implying a complete response , while the remaining 4 patients showed bcr / abl fusion signals that represent residual disease . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
A rare , in frame BCR ABL fusion ( e13a3 ) in a patient with an aggressive chronic myeloid leukaemia . ^^^ We have identified a rare BCR ABL chimaeric gene with multiplex and nested RT PCR in a patient with an unusually aggressive chronic myeloid leukaemia . cDNA sequencing showed an in frame rearrangement with a breakpoint in BCR exon e 13 ( b 2 ) and fusion with ABL exon 3 following skipping of the entire ABL exon a 2 . ^^^ These data confirm the heterogeneity of breakpoints in BCR ABL rearrangements . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Role of the three dimensional distribution of abl and bcr genes in the formation of bcr / abl fusion gene in interphase neucleus . ^^^ OBJECTIVE : To explore the mechanism of bcr / abl fusion gene formation in view of its biological stereology . ^^^ METHODS : Assisted by fluorescent in situ hybridization combined with confocal laser scanning microscopy , we observed the effect of gamma ray exposure on three dimensional distribution of bcr and abl genes in the interphase nucleus of IM 9 cell line . ^^^ RESULTS : In interphase nuclei of IM 9 cells , abl and bcr genes retained their own definite distribution patterns that were dynamically and regularly modulated along with the phases of the cell cycle . gamma ray exposure , however , produced shortened distances between the 2 genes . ^^^ CONCLUSION : The accessibility of abl and bcr genes to each other in the interphase nuclei is one of the factors for bcr / acl fusion gene formation . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Location of the BCR / ABL fusion genes on both chromosomes 9q34 in Ph negative chronic myeloid leukemia . ^^^ We present two patients with Ph negative chronic myeloid leukemia ( CML ) and fusion signal BCR / ABL on both chromosomes 9 , located in region 9q34 . ^^^ Molecular studies ( RT PCR ) revealed the rearrangement in the major BCR region and expression of chimeric BCR / ABL mRNA of b3a2 configuration . ^^^ FISH studies revealed the BCR / ABL fusion signals on both chromosomes 9 and green BCR signals on both chromosomes 22 in all mitoses studied . ^^^ Quantitative assessment of BCR / ABL transcript level by RT PCR showed 60 and 70 % BCR / ABL positivity in two peripheral blood samples at 6 , 5 and 10 , 5 months after diagnosis , respectively , which does not correspond to the expression from two identical BCR / ABL hybrid genes . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic myeloid leukaemia ( CML ) is caused by the product of the BCR ABL oncogene , located on the Philadelphia ( Ph ) chromosome . ^^^ BCR ABL is generated as a result of a reciprocal t ( 9 ; 22 ) chromosomal translocation . ^^^ BCR ABL fusion transcripts can be detected by a sensitive reverse transcription polymerase chain reaction ( RT PCR ) in the leucocytes of some healthy individuals suggesting that chromosomal translocations may occur frequently in the general population . ^^^ The presence of BCR ABL fusion transcripts does not imply that the individual will inevitably develop CML since other conditions must be favourable for expansion of the abnormal clone . ^^^ BCR ABL fusion transcripts lack ABL exon a 1 and consist of BCR exons fused directly to ABL exon a 2 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic myeloid leukemia shown to be associated with the Ph translocation , characterised as a t ( 9 ; 22 ) , joins the bcr and abl genes and leads to expression of chimeric BCR ABL protein with enhanced tyrosine kinase ( TK ) activity . ^^^ The specific inhibitor of BCR ABL TK , STI 571 was developed by Brian Druker and his co workers in 1996 . ^^^ STI 571 ( Signal Transduction Inhibitor ) occupies the kinase pocket of the BCR ABL protein , and blocks ATP binding , thereby preventing phosphorylation of any substrate . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
METHODS : As bcr abl fusion gene plays an important role in CML pathology , three single unit ribozymes were designed and synthesized in 44 base pairs near the fusion point , two enzyme cleavage sites on bcr gene and one on abl gene . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Philadelphia chromosome positive chronic myeloid leukemia expressing p 190 ( BCR ABL ) . ^^^ We describe a case of Philadelphia chromosome positive chronic myeloid leukemia ( Ph positive CML ) expressing p 190 ( BCR ABL ) . ^^^ Reverse transcription polymerase chain reaction ( RT PCR ) analysis of bone marrow cells showed a 472 bp band using primers specific for the p 190 ( BCR ABL ) but not p 210 ( BCR ABL ) transcript . ^^^ Sequencing analysis revealed that the PCR product was derived from the fusion between BCR exon e 1 and ABL exon a 2 ( e1a2 ) . ^^^ CML expressing p 190 ( BCR ABL ) is relatively rare . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Bcr : a negative regulator of the Bcr Abl oncoprotein in leukemia . ^^^ The fusion of 5 ' parts of the BCR gene to the ABL gene at the second exon yields several forms of an oncogenic Bcr Abl oncoprotein observed in several types of Philadelphia chromosome positive leukemia patients . ^^^ The first exon of the BCR gene is a critical part of this fusion , as the coiled coil domain at the amino terminal domain of the Bcr protein causes oligomerization of the Bcr Abl oncoprotein forming tetramers , thereby activating the tyrosine kinase activity of the normally silent c Abl protein . ^^^ Another consequence of this Bcr Abl fusion is the extensive autophosphorylation of the cis Bcr protein sequences on tyrosine residues . ^^^ This review will summarize the effects of Bcr Abl autophosphorylation on tyrosines as they relate to the oncogenic activity of Bcr Abl , and as a means to inactivate the serine / threonine kinase activity of the Bcr protein . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BCR / ABL genes and leukemic phenotype : from molecular mechanisms to clinical correlations . ^^^ This chromosomal translocation results in the fusion between the 5 ' part of BCR gene , normally located on chromosome 22 , and the 3 ' part of the ABL gene on chromosome 9 giving origin to a BCR / ABL fusion gene which is transcribed and then translated into a hybrid protein . ^^^ Three main variants of the BCR / ABL gene have been described , that , depending on the length of the sequence of the BCR gene included , encode for the p 190 ( BCR / ABL ) , P 210 ( BCR / ABL ) , and P 230 ( BCR / ABL ) proteins . ^^^ Herein we review the data on the correlations between the type of BCR / ABL gene and the corresponding leukemic clinical features . ^^^ Lastly , drawing on experimental data , we provide insight into the different transforming power of the three hybrid BCR / ABL proteins . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The interaction of the Bcr Abl tyrosine kinase with the Src kinase Hck is mediated by multiple binding domains . ^^^ Bcr Abl is found in more than 95 % of cases with CML . ^^^ The mechanism of Bcr Abl induced transformation is not fully understood . ^^^ Bcr Abl is a constitutively active tyrosine kinase with transforming capacity for hematopoietic cells . ^^^ We demonstrated recently that the Src kinase Hck interacts directly with Bcr Abl by a kinase independent mechanism . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Bcr is a multifunctional protein that is the fusion partner for Abl ( p 210 Bcr Abl ) in Philadelphia chromosome positive leukemias . ^^^ These data indicate that Bcr is a novel regulator of c Myc function whose disrupted expression may contribute to the high level of c Myc protein that is observed in Bcr Abl transformed cells . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Fluorescence in situ hybridzation analysis showed no Philadelphia chromosome positive ( Ph+ ) cells in the peripheral blood at last ( FISH ) follow up , but BCR / ABL remained detectable . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Diversity of BCR and ABL gene breakpoints in chronic myelogenous leukemia ] . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The Philadelphia chromosome translocation ( t ( 9 ; 22 ) ) results in the molecular juxtaposition of two genes , BCR and ABL , to form an aberrant BCR ABL gene on chromosome 22 . ^^^ BCR ABL is critical to the pathogenesis of chronic myelogenous leukemia and a subset of acute leukemias . ^^^ The chimeric Bcr Abl protein has constitutively elevated tyrosine phosphokinase activity . ^^^ This abnormal enzymatic activation is critical to the oncogenic potential of Bcr Abl . ^^^ This paper reviews the current knowledge on the function of Bcr Abl and its normal counterparts ( Bcr and Abl ) , as well as the impact of this knowledge on the development of a remarkably successful targeted therapy approach . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic myeloid leukemia ( CML ) is a biphasic hematopoietic malignancy associated with a single cytogenetic aberration , the Philadelphia translocation t ( 9 ; 22 ) ( q 34 ; q 11 ) , resulting in the BCR ABL 1 fusion oncogene . ^^^ Amplifications of BCR ABL 1 were also detected and quantified in four CML cell lines by use of MAPH probes specific for ABL 1 exon 11 and BCR exon 1 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Increased adhesion was mediated by 3 domains : ( 1 ) the N terminal coiled coil domain that facilitates oligomerization and F actin localization ; ( 2 ) bcr sequences between aa 163 to 210 ; and ( 3 ) F actin localization through the C terminal actin binding domain of c abl . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Targeting of the N terminal coiled coil oligomerization interface of BCR interferes with the transformation potential of BCR ABL and increases sensitivity to STI 571 . ^^^ Translocations involving the abl locus on chromosome 9 fuses the tyrosine kinase c ABL to proteins harboring oligomerization interfaces such as BCR or TEL , enabling these ABL fusion proteins ( 10 ABL ) to transform cells and to induce leukemia . ^^^ To investigate the role of oligomerization for the transformation potential of 10 ABL and for the sensitivity to STI 571 , we constructed ABL chimeras with oligomerization interfaces of proteins involved in leukemia associated translocations such as BCR , TEL , PML , and PLZF . ^^^ We assessed the capacity of these chimeras to form high molecular weight ( HMW ) complexes as compared with p 185 ( BCR ABL ) . ^^^ The targeting of the oligomerization interface of p 185 ( BCR ABL ) by a peptide representing the coiled coil region of BCR reduced its potential to transform fibroblasts and increased sensitivity to STI 571 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Molecular mechanisms of transformation by the BCR ABL oncogene . ^^^ The BCR ABL oncogene is generated by the Philadelphia chromosome ( Ph ) translocation , fusing the BCR gene to the ABL gene . ^^^ The BCR ABL fusion protein has elevated ABL tyrosine kinase activity that is critical for transformation of hematopoietic cells . ^^^ Chronic myelogenous leukemia ( CML ) cells transformed by BCR ABL show reduced growth factor requirements and apoptosis , as well as enhanced viability and altered adhesion . ^^^ This review describes molecular mechanisms that are thought to be important for transformation by the BCR ABL oncoprotein and points at pathways for targeted drug development in the treatment of CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Late appearance of Philadelphia chromosome with the p 190 BCR / ABL chimeric transcript in acute myelogenous leukemia progressing from myelodysplastic syndrome ] . ^^^ We report a late appearance of the Philadelphia chromosome ( Ph ) with the p 190 BCR / ABL chimeric transcript in a 69 year old patient with acute myelogenous leukemia ( AML ) that had evolved from myelodysplastic syndrome ( MDS ) . ^^^ The fusion of the BCR and ABL genes was confirmed by fluorescence in situ hybridization analysis , and the reverse transcription polymerase chain reaction analysis further revealed the presence of the p 190 BCR / ABL chimeric transcript . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Fluorescence in situ hybridization ( FISH ) analysis has shown previously that 10 15 % of chronic myeloid leukemias ( CML ) have hemizygous deletions of variable sizes affecting regions that flank the ABL and BCR translocation breakpoints on the derivative chromosome 9 , and these patients have a poor outcome . ^^^ FISH studies using large commercial genomic probes have previously suggested that haploinsufficiency of sequences flanking either ABL or BCR modify the disease process of CML and lead to an unfavorable prognosis . ^^^ Detailed mapping of the 25 Q PCR microdeletions showed that the minimal deleted region extended approximately 120 kb from the 5 ' end of the ABL gene in the centromeric direction on the derivative chromosome 9 , and the region 3 ' to BCR on chromosome 22 was excluded . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
To elucidate the role of mitogen activated protein kinases ( MAPKs ) and Akt kinase in leukemogenesis caused by the breakpoint cluster region ( BCR ) Abelson ( ABL ) tyrosine kinase oncoprotein , we examined the activities of MAPKs and Akt kinase and their roles in the action of STI 571 , a specific inhibitor of BCR ABL tyrosine kinase , in chronic myelogenous leukemia ( CML ) cells . ^^^ These findings suggest that STI 571 does not effectively block signaling molecules downstream of the BCR ABL tyrosine kinase in some cases of CML blast crisis . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Extensive data indicate that the transcription factor NF kappa B is activated by signals downstream of oncoproteins such as Ras or breakpoint cluster region ( BCR ) ABL . ^^^ Consistent with this , evidence has been presented that NF kappa B activity is required for Ras and BCR ABL to transform cells . ^^^ The data presented here indicate that BCR ABL expression in 32D myeloid cells or oncogenic Ras expression in murine fibroblasts blocks the ability of tumor necrosis factor ( TNF ) to activate NF kappa B . ^^^ These studies suggest that the ability of Ras and BCR ABL to activate NF kappa B involves an uncharacterized pathway that does not involve classic IKK activity and that suppresses the TNF induced IKK pathway through a Raf / MEK / Erk independent mechanism . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic myeloid leukemia ( CML ) is characterized by the Philadelphia translocation that fuses BCR sequences from chromosome 22 upstream of the ABL gene on chromosome 9 . ^^^ The chimerical Bcr Abl protein expressed by CML cells has constitutive tyrosine kinase activity , which is essential for the pathogenesis of the disease . ^^^ Imatinib , an ATP competitive selective inhibitor of Bcr Abl , has unprecedented efficacy for the treatment of CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Here , we demonstrate that , like c Abl , Bcr Abl is negatively regulated through its SH 3 domain . ^^^ Kinase activity , transformation , and leukemogenesis by Bcr Abl are greatly impaired by mutations of the Bcr coiled coil domain that disrupt oligomerization , but restored by an SH 3 point mutation that blocks ligand binding or a complementary mutation at the intramolecular SH 3 binding site defined in c Abl . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Here , we review the functions , signaling activities , mechanism of transformation , and therapeutic targeting of two prototypic tyrosine kinase oncogenes , BCR ABL and FLT 3 , associated with chronic myeloid leukemia ( CML ) and acute myeloid leukemia ( AML ) , respectively . ^^^ BCR ABL is generated by the Philadelphia chromosome translocation between chromosomes 9 and 22 , creating a chimeric oncogene in which the BCR and c ABL genes are fused . ^^^ The product of this oncogene , BCR ABL , has elevated ABL tyrosine kinase activity and transforms hematopoietic cells by exerting a wide variety of biological effects , including reduction in growth factor dependence , enhanced viability , and altered adhesion of chronic myelocytic leukemia ( CML ) cells . ^^^ Elevated tyrosine kinase activity of BCR ABL is critical for activating downstream signalling cascades and for all aspects of transformation , explaining the remarkable clinical efficacy of the tyrosine kinase inhibitor , imatinib mesylate ( STI 571 ) . ^^^ As is the case for BCR ABL , these mutations activate the kinase activity constitutively , activate multiple signaling pathways , and result in an augmentation of proliferation and viability . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
One of these enzymes , the Bcr Abl oncoprotein , results from the fusion of the BCR and ABL genes that result from the reciprocal chromosomal translocation that forms the Philadelphia chromosome . ^^^ ABL is the cellular homologue of the oncogene found in murine Abelson leukemia virus , and BCR refers to breakpoint cluster region . ^^^ The Bcr Abl oncoprotein exhibits elevated protein tyrosine kinase activity , which is strongly implicated in the mechanism of development of chronic myeloid leukemia . ^^^ Resistance to STI 571 is often the result of mutations in residues of the Bcr Abl kinase that ordinarily bind to the drug . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Bcr Abl mediated resistance to apoptosis is independent of PI 3 kinase activity . ^^^ The Bcr Abl tyrosine kinase is responsible for the oncogenic phenotype observed in Philadelphia chromosome positive leukemia and induces resistance to apoptotic cell death in a variety of cell types . ^^^ Recent evidence supports the hypothesis that these two properties of Bcr Abl are derived from cooperative but distinct signaling pathways . ^^^ Phosphatidylinositol 3 kinase ( PI3K ) , which has been suggested to associate with and become activated by Bcr Abl , has been shown to be required for Bcr Abl mediated cell growth . ^^^ We therefore examined the role of PI 3 kinase in the anti apoptotic effect of Bcr Abl . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Real time PCR quantification of bcr / abl chimera and WT 1 genes in chronic myeloid leukemia ] . ^^^ In this study , we have developed RT PCR methods using real time PCR detection system , a LightCycler , for quantification of bcr / abl chimerical genes in peripheral blood and bone marrow of chronic myeloid leukemia patients . ^^^ Bcr / abl and WT 1 genes could be measured from 10 ( 2 ) to 10 ( 8 ) copies and 10 to 10 ( 5 ) copies with linearity , respectively . ^^^ Using real time PCR detection with LightCycler system , 2 10 10 ( 3 ) K 562 cells among 2 10 10 ( 6 ) total cells demonstrated the bcr / abl gene , while 2 10 10 ( 1 ) K 562 cells among 2 10 10 ( 6 ) total cells could be detected using the nested PCR method . ^^^ In tests of seven clinical samples , five samples demonstrated bcr / abl and WT 1 genes , while those in two other patients after bone marrow transplantation and a normal subject could not detected . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In most cases , it results from the reciprocal t ( 9 ; 22 ) ( q 34 ; q 11 ) , with the ABL proto oncogene from 9q34 fused to the breakpoint cluster region ( BCR ) locus on 22q11 . ^^^ FISH with breakpoint spanning probes for the BCR and ABL genes revealed information about the genesis of complex Ph translocations . ^^^ Lack of signals indicates deletions of parts of the BCR and ABL genes or of adjacent regions ( case 3 ) . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Protein kinase CKIIalpha interacts with the Bcr moiety of Bcr / Abl and mediates proliferation of Bcr / Abl expressing cells . ^^^ The Bcr protein was originally identified because of its fusion to Abl as a consequence of the Philadelphia chromosome translocation found in chronic myelogenous and acute lymphoblastic leukemias . ^^^ The Bcr moiety is essential for the transforming activity of the Bcr / Abl oncogene . ^^^ In search of physiologically relevant Bcr and Bcr / Abl interacting proteins , we performed an interaction screen in yeast using the entire Bcr protein as bait . ^^^ Inhibition of Bcr / Abl P 190 in lymphoma cells from Bcr / Abl transgenic mice using imatinib reduced CKIIalpha activity . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Fluorescent in situ hybridization ( FISH ) with whole chromosome paints and BCR ABL probes was used to confirm and / or complete the banding findings when a variant or a masked Philadelphia chromosome ( Ph ) translocation was found . ^^^ The BCR ABL fusion gene was detected on the Ph chromosome in all eight cases ; two cases presented also a deletion of the 5 ' ABL region on the derivative chromosome 9 . ^^^ In the five way translocation , the 3 ' DNA sequence of the ABL oncogene was fused with the 5 ' DNA sequence of the BCR gene on the Ph chromosome and the 5 ' end of ABL was inserted into the other chromosome 22 . ^^^ A masked Ph chromosome was identified in one of the 112 patients ; it involved the insertion of the 3 ' ABL into BCR on an apparently normal chromosome 22 , resulting in the BCR ABL fusion gene . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic myelogenous leukemia with e13a3 ( b2a3 ) type of BCR ABL transcript having a DNA breakpoint between ABL exons a 2 and a 3 . ^^^ We describe a patient with chronic myelogenous leukemia ( CML ) , in whom the DNA breakpoint in the BCR ABL fusion gene was determined to result in a rare e13a3 ( b2a3 ) transcript . ^^^ The breakpoint in BCR was intron 13 , which was 30 bp downstream from exon 13 , and the breakpoint in ABL was intron 2 , and was 46 bp downstream from exon a 2 . ^^^ This is the first report of BCR a 3 type CML in which the exact DNA breakpoint was identified and located between exons a 2 and a 3 of the ABL gene . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The Philadelphia chromosome found in leukemia cells of chronic myelogenous leukemia ( CML ) patients is produced by translocation between chromosomes 9 and 22 , resulting in expression of a chimera protein of Bcr and Abl kinase in the cytoplasm . ^^^ Bcr Abl kinase attracted oncology researchers as a molecular target for CML therapy , and a variety of small Abl kinase inhibitors were synthesized . ^^^ STI 571 competitively binds to the ATP binding site of Bcr Abl kinase and inhibits Abl tyrosine kinase activity . ^^^ Certain point mutations in the ATP binding site were found to be a cause of resistance to STI 571 in both Bcr Abl and c Kit kinases . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
A novel tricolor , dual fusion fluorescence in situ hybridization method to detect BCR / ABL fusion in cells with t ( 9 ; 22 ) ( q 34 ; q11 . 2 ) associated with deletion of DNA on the derivative chromosome 9 in chronic myelocytic leukemia . ^^^ Dual color , dual fusion fluorescence in situ hybridization ( D FISH ) can accurately detect and quantify cells with BCR / ABL fusion in < 1 % of 500 nuclei in 80 % of patients with chronic myelocytic leukemia ( CML ) and t ( 9 ; 22 ) ( q 34 ; q11 . 2 ) . ^^^ Neoplastic cells with one ABL , one BCR , and one BCR / ABL fusion are particularly problematic , because normal cells with coincidental overlap have the same pattern . ^^^ We tested a new method that incorporates an aqua labeled probe for the argininosuccinate synthetase ( ASS ) gene into the conventional BCR / ABL D FISH probe set . ^^^ We used TD FISH to study 20 normal specimens and 35 specimens from 20 patients with known loss of both BCR and ABL from the derivative chromosome 9 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In this case , fluorescence in situ hybridization and reverse transcriptase polymerase chain reaction showed a normal pattern for BCR and ABL genes , suggesting that a different and unrelated clone developed after the disappearance of the Ph chromosome . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The discovery two decades ago that the Philadelphia chromosome encodes an oncogenic fusion of Bcr and Abl remains among the most important contributions to our understanding of the process of malignant transformation . ^^^ We now know that Bcr Abl is one of more than 30 aberrantly activated tyrosine kinases that are expressed in a variety of tumors . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Specific killing of Ph+ chronic myeloid leukemia cells by a lentiviral vector delivered anti bcr / abl small hairpin RNA . ^^^ Chronic myeloid leukemia ( CML ) is characterized by a reciprocal chromosomal translocation between chromosomes 9 and 22 t ( 9 ; 22 ) ( q 34 ; q 11 ) that causes fusion of the bcr and abl genes . ^^^ Transcription and splicing of the fusion gene generate two major splice variants of the bcr / abl transcript that encode an oncoprotein with tyrosine kinase activity . ^^^ We have taken advantage of lentiviral vectormediated delivery of anti bcr / abl short hairpin RNAs ( shRNA ) to downregulate the bcr / abl transcript in Philadelphia chromosome positive ( Ph+ ) K 562 leukemia cells . ^^^ This downregulation caused complete inhibition of proliferation of these cells and was accompanied by > 90 % inhibition of the bcr / abl transcript and p 210 protein . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
At the molecular level this involves the fusion of the ABL protooncogene on chromosome 9 with the BCR ( breakpoint cluster region ) gene on chromosome 22 . ^^^ Diagnosis of CML is based on the peripheral blood smear , bone marrow examination , the presence of the Philadelphia chromosome and its molecular correlate , the BCR ABL transcript . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We report a case of BCR ABL negative atypical chronic myeloid leukemia ( CML ) with translocation t ( 4 ; 22 ) ( q 12 ; q11 . 2 ) juxtaposing the breakpoint cluster region ( BCR ) and platelet derived growth factor receptor alpha ( PDGFRA ) genes . ^^^ Initial cytogenetic evaluation by interphase FISH for BCR ABL , to rule out a translocation 9 ; 22 , showed a variant signal pattern consistent with rearrangement of BCR at 22q11 . 2 , but not ABL at 9q34 . ^^^ Analysis of the patient ' s cDNA by polymerase chain reaction ( PCR ) for BCR ABL was negative . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The resulting fusion of the BCR and ABL 1 loci produces the constitutively active BCR / ABL1 tyrosine kinase . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic myeloid leukemia with an e13a3 BCR ABL fusion : benign course responsive to imatinib with an RT PCR advisory . ^^^ A case of a patient with chronic myeloid leukemia whose cells expressed an e13a3 ( b2a3 ) variant BCR ABL p 210 mRNA is presented . ^^^ The variant splice was detected by a qualitative reverse transcriptase polymerase chain reaction using primers complementary to BCR exon 13 ( b 2 ) and ABL exon 3 ( a 3 ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Second case of CML with aberrant BCR ABL fusion transcript ( e8 / a2 ) with insertion of an inverted ABL intron 1b sequence . ^^^ We found a case of Ph positive chronic myelogenous leukemia ( CML ) patient with an atypical BCR ABL transcript that was undetectable by a routine reverse transcription polymerase chain reaction ( RT PCR ) for major BCR ABL . ^^^ Additional RT PCR and sequence analyses have demonstrated that the aberrant transcript consists of a fusion of BCR exon 8 ( e 8 ) and ABL exon 2 ( a 2 ) with an insertion of a 55 bp inverted sequence of intron 1b between them . ^^^ These are the only two CML cases in the literature with identical aberrant BCR ABL transcripts . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Interference of BCR ABL 1 kinase activity with antigen receptor signaling in B cell precursor leukemia cells . ^^^ The chromosomal translocation t , ( 9 ; 22 ) resulting in the fusion of the BCR and ABL 1 genes , represents a recurrent aberration in B cell precursor leukemia cells . ^^^ Unexpectedly , B cell precursor leukemia cells harboring a BCR ABL 1 gene rearrangement do not depend on antigen receptor mediated survival signals . ^^^ However , upon inhibition of the BCR ABL 1 kinase activity by STI 571 , only leukemia cells expressing an antigen receptor are able to survive . ^^^ Since resistance to STI 571 is frequent in the therapy of BCR ABL 1 ( + ) B cell precursor leukemia , antigen receptor signaling may represent a mechanism through which these cells can temporarily evade STI 571 induced apoptosis . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
An example is provided by chronic myeloid leukemia ( CML ) cells , most of which carry a translocation involving the ABL gene on chromosome 9 and the BCR gene on chromosome 22 . ^^^ The hypothesis of a causal relationship between CML and the chimeric protein product of the BCR ABL translocation has recently received strong support . ^^^ As an application , yields of BCR ABL translocations were calculated . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Insertion of a genomic fragment of chromosome 19 between BCR intron 19 and ABL intron 1a in a chronic myeloid leukaemia patient with micro BCR ABL ( e19a2 ) transcript . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Quantitative monitoring of BCR ABL transcript suggestion of a simplified approach considering inaccuracy of measurement and calibration . ^^^ According to standard protocols , real time quantitative RT PCR ( RQ PCR ) for quantification of BCR ABL fusion transcripts in CML patients is performed with the construction of a standard curve for each run , each sample is analyzed at least in duplicate and 10 40 ml peripheral blood are processed . ^^^ Finally , we propose a standardized collection and isolation of total RNA from only 2 . 5 ml blood using an integrated system , which allows RNA stabilization for up to 5 days and provides snapshots of BCR ABL fusion transcripts with higher accuracy than with non stabilized blood samples . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
AIMS : Our objective was to establish a multiplexed assay using the Biomed 1 primers to detect AML 1 ETO transcripts and 10 different CBFB MYH 11 transcripts , using BCR and ABL transcripts as controls . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Influence of BCR / ABL fusion proteins on the course of Ph leukemias . ^^^ This gene rearrangement results in the production of a novel oncoprotein , BCR / ABL , a constitutively active tyrosine kinase . ^^^ There is compelling evidence that the malignant transformation by BCR / ABL is critically dependent on its Abl tyrosine kinase activity . ^^^ We supposed that additional mutations accumulate in this region of the BCR / ABL oncogene during the development of the malignant blast crisis in CML patients . ^^^ Sequencing of PCR product of the BCR / ABL gene ( Dbl , PH region ) showed that along with single nucleotide substitutions other mutations , mostly deletions , had occurred . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The cytogenetic hallmark of CML , the Ph chromosome with the molecular juxtaposition of BCR and ABL genes and the multistep pathogenesis with the stable chronic phase , the accelerated phase and the terminal blast crisis provide the background for the translation of molecular cytogenetic findings into clinical practice . ^^^ The systematic development of the selective BCR ABL inhibitor imatinib was based on the discovery of the molecular pathogenesis of CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Fluorescent in situ hybridization analysis of Philadelphia chromosome negative chronic myeloid leukemia with the bcr / abl fusion gene . ^^^ This report describes a patient with Philadelphia chromosome negative ( Ph ) but bcr / abl fusion gene positive chronic myeloid leukemia ( CML ) and a molecular analysis of the mechanisms behind the Ph status . ^^^ Spectral karyotyping fluorescent in situ hybridization ( SKY FISH ) analysis showed no abnormal translocation ; however , a bcr / abl fusion gene was detected by reverse transcriptase polymerase chain reaction analysis . ^^^ On the other hand , FISH analysis of the abl and bcr genes with dual fusion probes , which can detect the bcr / abl fusion gene on both the der ( 9 ) and der ( 22 ) chromosomes , showed the signal for bcr / abl fusion on the der ( 22 ) chromosome but not on the der ( 9 ) chromosome . ^^^ These results indicate that insertion of the abl gene into the bcr region on the der ( 22 ) chromosome or retranslocation between the der ( 9 ) chromosome and the der ( 22 ) chromosome may have caused the Ph CML in this case . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Characterization of the different BCR ABL transcripts with a single multiplex RT PCR . ^^^ The diagnosis of chronic myeloid leukemia is based on detection of the Philadelphia ( Ph ) chromosome or the BCR ABL gene . ^^^ We have developed a clinical molecular diagnosis assay , able to identify all of the BCR ABL transcripts and , by single assay , to characterize all of the possible transcript junctions . ^^^ For each patient sample , we performed RT PCR with three different BCR primers each coupled to a specific different fluorochrome and a unique reverse ABL primer . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
To evaluate the frequency of cytogenetically undetectable abnormalities , we performed fluorescence in situ hybridization ( FISH ) analyses in 273 AML M 0 M2 with normal karyotype using probes for ETO , ABL , MLL , TEL , RB , P 53 , AML 1 , and BCR . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Modulation of the p 38 MAPK ( mitogen activated protein kinase ) pathway through Bcr / Abl : implications in the cellular response to Ara C . ^^^ The chimaeric protein Bcr / Abl , the hallmark of chronic myeloid leukaemia , has been connected with several signalling pathways , such as those involving protein kinase B / Akt , JNK ( c Jun N terminal kinase ) or ERKs ( extracellular signal regulated kinases ) 1 and 2 . ^^^ Here , we present evidence showing that Bcr / Abl is able to modulate this signalling pathway . ^^^ Transient transfection experiments indicated that overexpression of Bcr / Abl in 293T cells is able to activate p 38 MAPK or induce p 73 stabilization , suggesting that c Abl and Bcr / Abl share some biological substrates . ^^^ Interestingly , the control exerted by Bcr / Abl on the p 38 MAPK pathway was not only mediated by the tyrosine kinase activity of Bcr / Abl , as the use of STI 571 demonstrated . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Global effects of BCR / ABL and TEL / PDGFRbeta expression on the proteome and phosphoproteome : identification of the Rho pathway as a target of BCR / ABL . ^^^ To identify commonalities and differences in the action of two such kinases , breakpoint cluster region ( BCR ) / ABL and TEL / PDGFRbeta , two dimensional gel electrophoresis was employed to characterize their effects on the proteome . ^^^ A number of proteins whose expression is altered by BCR / ABL , including gelsolin and stathmin , are related to cytoskeletal function whereas no such changes were seen in TEL / PDGFRbeta transfected cells . ^^^ Correspondingly , BCR / ABL transfected cells were less responsive to chemotactic and chemokinetic stimuli than non transfected cells and TEL / PDGFRbeta transfected Ba / F3 cells . ^^^ A phosphoprotein specific gel stain was used to identify TEL / PDGFRbeta and BCR / ABL mediated changes in the phosphoproteome . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Fluorescence in situ hybridization characterization of different cryptic BCR ABL rearrangements in chronic myeloid leukemia . ^^^ Using fluorescence in situ hybridization probes , obtained from bacterial artificial chromosome ( BAC ) libraries that relate to sequences either side of the BCR and ABL genes , this study characterized four chronic myeloid leukemia cases with cryptic BCR ABL rearrangements . ^^^ Each case showed evidence of a different underlying mechanism : one case showed a microinsertion of BCR into ABL , another a microinsertion of ABL into BCR , and the third showed a complex rearrangement including deletion of adjacent flanking sequences , consistent with the reverse translocation model of cryptic rearrangement . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The significance of these findings is discussed here in the context of aging and tumorigenesis and their links to reactive oxygen species . c Abl and its derivatives BCR ABL and 5 Abl were discovered more than twenty years ago . ^^^ BCR ABL and 5 Abl acquire elevated tyrosine kinase activities by fusing to BCR and gag respectively and are capable of transforming myeloid and fibroblast cells . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Here , we examined the effect of OSU 03012 , a celecoxib derived phosphoinositide dependent kinase 1 ( PDK 1 ) inhibitor , on imatinib mesylate induced apoptosis in 2 clinically relevant breakpoint cluster region ( Bcr ) Abl mutant cell lines , Ba / F3p210 ( E255K ) and Ba / F3p210 ( T315I ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The BCR ABL 1 fusion kinase is frequently associated with chronic myeloid leukemia and B cell acute lymphoblastic leukemia but is rare in T cell acute lymphoblastic leukemia ( T ALL ) . ^^^ EML 1 ABL1 and breakpoint cluster region ( BCR ) ABL 1 were equally sensitive to the tyrosine kinase inhibitor imatinib . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Interpretation of submicroscopic deletions of the BCR or ABL gene should not depend on extra signal FISH : problems in interpretation of submicroscopic deletion of the BCR or ABL gene with extra signal FISH . ^^^ To assess the variation between detection methods in the interpretation of a submicroscopic gene deletion , we performed an extra signal ( ES ) FISH BCR / ABL and double FISH ( D FISH ) BCR / ABL on frozen bone marrow cells from 79 patients with CML ( 63 in the chronic phase , 6 in the accelerated phase , and 10 in blast crisis ) and 30 patients with a BCR / ABL negative myeloproliferative disorder as determined by RT PCR . ^^^ The cutoff values for false positive signals from a juxtaposition of the BCR and ABL gene were 11 % in ES FISH and 13 % in D FISH . ^^^ Of the 14 patients who showed an ABL gene deletion by ES FISH , 5 had an ABL deletion only , 5 had both a BCR and an ABL deletion , but 4 proved to have a classic BCR / ABL rearrangement without a submicroscopic deletion , as determined by D FISH . ^^^ In conclusion , an interpretation of the submicroscopic deletions of the BCR or ABL gene should not depend on ES FISH . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The translocation result the fusion of the ABL gene located at the long arm of chromosome 9 with the BCR gene located at the long arm of chromosome 22 . ^^^ The BCR / ABL fusion gene encodes a chimeric protein with elevated tyrosine kinase activity , that plays an important role in the pathogenesis of the disease . ^^^ In the diagnosis of chronic myelogenous leukemia and in the evaluation of the therapeutic effect , the detection of the t ( 9 ; 22 ) ( q 34 ; q 11 ) translocation and BCR / ABL fusion gene plays an important role . ^^^ The authors in the present paper provides a review on the recently used methods of the detection of t ( 9 ; 22 ) ( q 34 ; q 11 ) chromosomal translocation and BCR / ABL fusion gene and their role in the diagnosis , monitoring and evaluation of therapeutic effect in chronic myelogenous leukemia . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The leukemogenic mechanisms of CML were hypothesized 20 years later when it was discovered that the t ( 9 ; 22 ) translocation produced a fusion gene involving the BCR gene from chromosome 22 and the ABL protooncogene from chromosome 9 [ corrected ] Multiple breakpoints in BCR produce fusion genes that are translated into chimeric protein products of different lengths that are associated with different leukemic subtypes . ^^^ However , it appears that CML results from a single mutagenic event involving the t ( 9 ; 22 ) translocation leading to the development of the BCR / ABL fusion gene and the corresponding fusion protein . ^^^ The successful transcription and translation of the BCR / ABL fusion protein led researchers to carefully study its involvement in leukemogenesis . ^^^ The BCR / ABL fusion protein exhibits increased and constitutive tyrosine kinase activity that differs depending on which BCR breakpoint is expressed , resulting in varying clinical presentations . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic myeloid leukemia is a clonal stem cell disease caused by an acquired somatic mutation that fuses , through chromosomal translocation , the abl and bcr genes on chromosomes 9 and 22 , respectively . ^^^ The bcr / abl gene product is an oncogenic protein that localizes to the cytoskeleton and displays an up regulated tyrosine kinase activity that leads to the recruitment of downstream effectors of cell proliferation and cell survival and consequently cell transformation . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Disease status in patients with chronic myeloid leukemia is better characterized by BCR ABL / BCR transcript ratio than by BCR ABL transcript level , which may suggest a role of normal BCR gene in the disease pathogenesis . ^^^ Monitoring of BCR ABL transcript level is widely used in chronic myeloid leukemia ( CML ) to follow up response to therapy . ^^^ In this study we compare abilities of two quantitative RT PCR assays to characterize the disease status in CML patients : RT PCR quantifying the BCR ABL transcript concentration and RT PCR determining the BCR ABL / BCR transcript ratio ( R ) . ^^^ We demonstrate that in non responders only R , but not BCR ABL , unambiguously characterizes the state of disease . ^^^ Moreover , R values > 1 found in all poor responders indicate lower BCR expression compared to BCR ABL in these patients . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Coexistence of different clonal populations harboring the b3a2 ( p 210 ) and e1a2 ( p 190 ) BCR ABL 1 fusion transcripts in chronic myelogenous leukemia resistant to imatinib . ^^^ In this study , we report the case of a Philadelphia ( Ph ) positive chronic myelogenous leukemia ( CML ) patient with the presence of p 190 and p 210 BCR ABL 1 mRNA fusion transcripts derived from e1a2 and b3a2 BCR ABL 1 genomic rearrangements , respectively . ^^^ The presence of e1a2 BCR ABL 1 genomic rearrangement was seen in 2 different clones , one with the rearrangement and another one with the rearrangement and deletion of the BCR gene of the non rearranged chromosome 22 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Nuclear topography and expression of the BCR / ABL fusion gene and its protein level influenced by cell differentiation and RNA interference . ^^^ Nuclear topography , expression of the BCR / ABL fusion gene and its protein level / cellular pattern were studied in CML cell line K 562 stimulated to differentiation , apoptosis and influenced by ABL RNA interference ( ABL RNAi ) . ^^^ Phorbol ester induced maturation of K 562 cells was accompanied by repositioning of down regulated BCR / ABL genes closer to the nuclear membrane . ^^^ This nuclear rearrangement could be connected with differentiation related heterochromatinization of the amplified BCR ABL locus , as demonstrated by increased histone H 3 ( K 9 ) dimethylation and decreased H 3 ( K 9 ) acetylation of B3A2 breakpoint . ^^^ Topography of BCR / ABL in differentiated K 562 cells was compared with other leukemic cell types : PMA maturation of HL 60 cells did not influence the nuclear positioning of individual BCR and ABL genes . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Distinguishing between proliferating nodal lymphoid blasts in chronic myelogenous leukemia and non Hodgkin lymphoma : report of three cases and detection of a bcr / abl fusion signal by single cell analysis . ^^^ Subsequently , bcr gene rearrangement and bcr / abl mRNA expression were detected by Southern blot and reverse transcription polymerase chain reaction analysis of the lymph nodes . ^^^ Fluorescence in situ hybridization ( FISH ) analysis of lymph node touch smears also disclosed bcr / abl gene fusion signals in the blasts of all patients , confirming that the blasts were derived from Philadelphia chromosome positive CML . ^^^ FISH analysis of bcr / abl in single cell blast preparations is an efficient tool that allows rapid , accurate cytopathological diagnosis of extramedullary blast phase CML and its discrimination from non Hodgkin lymphoma . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We also showed that separate clustering of samples with the BCR / ABL translocation could be explained by different breakpoint regions in the BCR . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
PURPOSE : We characterized the clinical course of renal medullary carcinoma ( RMC ) and performed an expanded analysis of BCR ABL . ^^^ BCR and ABL genes , and ABL protein were evaluated by fluorescence in situ hybridization and immunohistochemical analysis , respectively . ^^^ No evidence of BCR ABL translocation was detected . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic myeloid leukemia ( CML ) is characterized by the presence of a t ( 9 ; 22 ) ( q 34 ; q11 . 2 ) , which leads to the well known BCR ABL 1 fusion protein . ^^^ Chromosomal fluorescence in situ hybridization showed that the BCR gene locus spanned the breakpoint at band 22q11 . 2 but that the ABL 1 gene was not rearranged . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
E6a2 BCR ABL fusion with BCR exon 5 deleted transcript in a Philadelphia positive CML responsive to Imatinib . ^^^ Chronic myeloid leukemia ( CML ) is characterized in 90 % of patients by the presence of the reciprocal translocation t ( 9 ; 22 ) ( q 34 ; q 11 ) leading to the fusion of the BCR and ABL genes . ^^^ We report here a sixth case of a Ph positive patient with an e6a2 BCR ABL fusion transcript and describe for the first time a chimeric molecule alternatively spliced for exon 5 of the BCR gene . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Bcr Abl activates the AKT / Fox O 3 signalling pathway to restrict transforming growth factor beta mediated cytostatic signals . ^^^ The fusion of Abl with either Bcr or Tel in human leukaemia leads to the constitutive activation of Abl tyrosine kinase , which in turn induces growth factor independent proliferation and cell survival . ^^^ However , the mechanism by which Bcr Abl induces cellular transformation has not yet been well characterized . ^^^ Here , we show that Bcr Abl expressing cells are resistant to growth inhibition and apoptosis mediated by transforming growth factor beta ( TGF beta ) . ^^^ Interestingly , we observed that the suppressive effects of Bcr Abl on TGF beta responses were not mediated by an impairment of Smad signalling , which is believed to act as the principal mediator of TGF beta responses . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Here we show that BCR independent aggregation of the Fc gammaRIIB 1 transduces an ITIM and SHIP independent proapoptotic signal that is dependent on members of the c Abl tyrosine kinase family . ^^^ These results define a novel Abl family kinase dependent Fc gammaRIIB 1 signaling pathway that functions independently of the BCR in controlling antigen driven B cell responses . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Fluorescence in situ hybridisation ( FISH ) analysis with locus specific probes for ABL at 9q34 [ bacterial artificial chromosomes ( BACs ) 835J22 and 1132H12 ] , IGH at 14q32 [ P 1 artificial chromosome ( PAC ) 998D24 ] and IGL ( PAC 1019H10 ) and BCR ( BAC 74M14 ) at 22q11 , as well as multicolour in situ hybridisation ( M FISH ) analyses were performed . ^^^ A three way variant translocation of the classical t ( 9 ; 22 ) ( q 34 ; q 11 ) , t ( 9 ; 22 ; 14 ) ( q 34 ; q 11 ; q 32 ) , involving both BCR and ABL , was unravelled by the molecular cytogenetic investigations in the three myeloid leukaemia cases ; a similar variant translocation has previously been reported in seven CML . ^^^ The two cases of NHL ( one NHL with a similar 14 ; 22 translocation has been reported previously ) had no involvement of BCR or ABL , but instead the IGH and IGL genes were shown to be juxtaposed by the t ( 14 ; 22 ) ( q 32 ; q 11 ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The incidence and patterns of BCR / ABL rearrangements in chronic myeloid leukaemia ( CML ) using fluorescence in situ hybridisation ( FISH ) . ^^^ INTRODUCTION : Chronic myeloid leukaemia ( CML ) is characterised by the formation of the BCR / ABL fusion gene , usually as a result of the Philadelphia ( Ph ) translocation between chromosomes 9 and 22 . ^^^ MATERIALS AND METHODS : The incidence of both typical and atypical BCR / ABL gene rearrangements was determined in 110 patients suspected of CML using dual fusion fluorescence in situ hybridisation ( DF FISH ) probes . ^^^ Fusion signals were detected in 57 . 1 % of CML Ph negative patients , indicating cryptic BCR / ABL rearrangements ( i . e . , masked Ph ) . ^^^ CONCLUSION : FISH is able to detect BCR / ABL fusion in CML with masked or variant Ph not apparent with conventional karyotyping . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
COMBO FISH for focussed fluorescence labelling of gene domains : 3D analysis of the genome architecture of abl and bcr in human blood cells . ^^^ To investigate the architecture of abl and bcr in blood cell nuclei forming the Philadelphia chromosome in CML , we applied COMBO FISH using specifically colocalising combinations of triple strand forming oligonucleotide probes for abl on chromosome 9 and bcr on chromosome 22 . ^^^ Measurements by 3D microscopy were compared to results obtained after standard FISH using commercially available abl / bcr BAC probes . ^^^ The relative radial fluorescence distributions in lymphocyte cell nuclei of healthy donors in comparison to cell nuclei of blood cells of CML patients showed a strong correlation in the location of abl and bcr for both labelling techniques . ^^^ The absolute distances of the homologous bcr domains and the abl domain nuclear center abl domain angles in cell nuclei of CML donors differed significantly from those of healthy donors only when COMBO FISH was applied . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BCR / ABL rearrangement in two cases of Philadelphia chromosome negative chronic myeloid leukemia : deletion on the derivative chromosome 9 may or not be present . ^^^ The BCR / ABL gene rearrangement is the causing factor in chronic myeloid leukemia ( CML ) . ^^^ About 5 10 % of CML patients lack cytogenetic evidence of the Ph translocation but show BCR / ABL fusion by fluorescence in situ hybridization ( FISH ) or reverse transcriptase polymerase chain reaction . ^^^ Deletions around the breakpoints on the derivative 9 including ABL and or BCR sequences occur in 10 15 % of Ph+ CML patients and are thought to have prognostic significance . ^^^ We describe two patients with CML and normal karyotype in whom cryptic rearrangements involving chromosomes 9 and 22 resulted in the causative BCR / ABL gene . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Karyotyping with conventional and multiplex fluorescence in situ hybridization ( FISH and M FISH ) karyotyping , complemented with reverse transcriptase polymerase chain reaction , identified a variant Philadelphia translocation t ( 9 ; 14 ; 22 ) ( q 34 ; q 32 ; q 11 ) involving a cryptic BCR / ABL fusion with formation of the p 190 ( Bcr Abl ) oncoprotein . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The unique molecular characteristic of chronic myeloid leukemia ( CML ) , the disease causing ABL ( 9q34 ) to BCR ( 22q11 ) translocation , has provided an invaluable tool for disease diagnosis and monitoring of treatment response . ^^^ However , this particular laboratory test misses submicroscopic BCR / ABL translocations and is suboptimal for minimal residual disease ( MRD ) assessment . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The first , established from pairs of translocated genes ( such as BCR and ABL ) , considers the spatial proximity of loci in interphase nuclei ( static `` contact first ' ' model ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Bcr abl translocation can occur during the induction of multidrug resistance and confers apoptosis resistance on myeloid leukemic cell lines . ^^^ RT PCR and Western blot analysis showed that this increase in Abl antigen content was accompanied by the expression in U 937 DR and HL 60 DR100 cells of a hybrid bcr / abl mRNA and a 210 kD Bcr / Abl protein which was constitutive in K 562 . ^^^ This expression was due to the translocation of abl and the amplification of the bcr abl translocated gene . ^^^ These results are in agreement with the role of Bcr / Abl tyrosine protein kinase as an inhibitor of apoptosis independently of the mdr 1 expression . ^^^ They also suggest that translocation of the abl gene in the bcr region is a highly probable rearrangement in the mdr 1 expressing myeloid cells and that Bcr / Abl tyrosine kinase effect on apoptosis needs the regulation of intracellular pH and is inactive against UV induced apoptosis . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Detection of BCR ABL mutations and resistance to imatinib mesylate . ^^^ The major mechanism of imatinib resistance for patients with chronic myeloid leukemia ( CML ) is clonal expansion of leukemic cells with mutations in the Bcr Abl fusion tyrosine kinase that reduce the capacity of imatinib to inhibit kinase activity . ^^^ Direct sequencing of the BCR ABL kinase domain is relatively rapid and allows detection of emerging mutations at a sensitivity of approx 20 % . ^^^ For optimal sensitivity , the kinase domain of the abnormal gene should be isolated by reverse transcription ( RT ) polymerase chain reaction ( PCR ) amplification using primers that hybridize to the BCR and ABL genes . ^^^ The quality of the RNA is assessed by real time quantitative PCR prior to analysis , and BCR ABL levels are determined . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Generation of the BCR / ABL fusion gene in a Philadelphia chromosome negative chronic myeloid leukaemia : insertion of 5 . 6 Mb of 9q34 into the BCR region of chromosome 22 . ^^^ This report describes a chronic myelogenous leukaemia patient with an apparently normal bone marrow karyotype but BCR / ABL fusion gene positive . ^^^ Commercial FISH probes showed an atypical pattern and the BCR / ABL fusion transcript was detected by RT PCR , but not the reciprocal ABL / BCR . ^^^ The ABL gene and the following 5 . 6 5 . 7 Mb of 9q are inserted into the BCR region of chromosome 22 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Virtually all patients with chronic myelogenous leukemia ( CML ) express an aberrant protein ( p 210 Bcr Abl ) that contains NH 2 terminal sequences from Bcr fused to COOH terminal sequences from Abl . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Forty six patients with chronic myeloid leukemia receiving imatinib mesylate ( 39 in chronic phase , one in accelerated phase , and six in blastic crisis ) , were studied for a 20 62 month follow up period by cytogenetics and fluorescence in situ hybridization using dual color , dual fusion BCR and ABL probes . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Deletion of any part of the BCR or ABL gene on the derivative chromosome 9 is a poor prognostic marker in chronic myelogenous leukemia . ^^^ To evaluate the prognostic significance of submicroscopic deletions of the ABL or BCR gene associated with t ( 9 ; 22 ) in chronic myelogenous leukemia ( CML ) , we investigated the incidence of an ABL or BCR deletion on derivative chromosome 9 using fluorescence in situ hybridization ( FISH ) . ^^^ FISH was performed using the LSI BCR / ABL dual fusion translocation probe on bone marrow cells of 86 patients with CML . ^^^ Of 86 patients , ABL deletion was detected in 13 ( 15 . 1 % ) patients and BCR deletion in 8 patients ( 9 . 3 % ) . ^^^ Patients with ABL and / or BCR deletion ( 14 / 86 patients , 16 . 3 % ) showed significantly short OS and EFS ( median OS , 43 . 0 months ; median EFS , 40 . 0 months ) , compared to the patients without any BCR or ABL gene deletions ( median OS , 94 . 0 months ; median EFS , 90 . 0 months ; P = 0 . 041 for OS , P = 0 . 008 for EFS ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
These studies revealed two primary points : ( 1 ) genomic microdeletions were concomitant with the t ( 9 ; 22 ) rearrangement ; and ( 2 ) the location of the deleted sequence was centromeric to ABL and telomeric to BCR genes . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic myeloid leukemia ( CML ) is caused by the constitutively activated tyrosine kinase breakpoint cluster ( BCR ) ABL . ^^^ Current frontline therapy for CML is imatinib , an inhibitor of BCR ABL . ^^^ Although imatinib has a high rate of clinical success in early phase CML , treatment resistance is problematic , particularly in later stages of the disease , and is frequently mediated by mutations in BCR ABL . ^^^ Dasatinib ( BMS 354825 ) is a multitargeted tyrosine kinase inhibitor that targets oncogenic pathways and is a more potent inhibitor than imatinib against wild type BCR ABL . ^^^ It has also shown preclinical activity against all but one of the imatinib resistant BCR ABL mutants tested to date . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Quantitative monitoring of breakpoint cluster region ( BCR ) Abelson kinase ( ABL ) transcripts has become indispensable in the clinical care of patients with chronic myelogenous leukemia . ^^^ Because quantity and quality of RNA in clinical samples are highly variable , a suitable internal normalization control is required for accurate BCR ABL quantification . ^^^ We also examined expression of the control genes in BCR ABL positive K 562 cells in response to Gleevec treatment . ^^^ Importantly , ABL , a widely used control gene , generates misleading BCR ABL changes that potentially affect the clinical management of chronic myelogenous leukemia patients . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The critical causative event in chronic myelogenous leukemia ( CML ) is the fusion of the head of the bcr gene with the body of the abl gene , named bcr / abl gene . ^^^ This chimeric BCR / ABL molecule transforms primary myeloid cells to leukemic cells and induces a CML like disease in mice . ^^^ The mouse CML model expressing the BCR / ABL molecule has provided important new insights into the molecular pathophysiology of CML and has directly answered many questions regarding this disease . ^^^ Furthermore , numerous clinical studies have demonstrated a correlation between leukemic clinical features and the position of the breakpoint in the BCR gene of the chimeric BCR / ABL gene . ^^^ The BCR / ABL molecule is unique oncogeneiety , having ABL tyrosine kinase activity , making it an ideal target for drug development . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Impact of BCR / ABL gene expression on the proliferative rate of different subpopulations of haematopoietic cells in chronic myeloid leukaemia . ^^^ Despite the effects of BCR ABL on cell proliferation , no study has compared the proliferative rate of different haematopoietic cell compartments from chronic myeloid leukaemia ( CML ) with those of normal bone marrow ( NBM ) . ^^^ We comparatively analysed the cell cycle distribution and BCR / ABL expression in different compartments of BM cells from 15 CML and 11 NBM . ^^^ In BM cells separated by fluorescence activated cell sorting , decreasing levels of BCR / ABL mRNA were found from CD34+ / CD38+ myeloid precursors to myeloblasts ; BCR / ABL expression increased afterwards with a peak at the myelocyte / metamyelocyte stage , decreasing in the more mature band / neutrophil compartment . ^^^ Unexpectedly , BCR / ABL gene expression showed an inverse correlation with the proportion of S + G2 / M phase cells ( R = 0 . 33 ; P = 0 . 04 ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The Philadelphia ( Ph ) chromosome usually results from the t ( 9 ; 22 ) , which causes the physical association of the BCR 1 and ABL genes and their function as a single new gene . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Overwhelming evidence indicates a role for the deregulated ABL protein tyrosine kinase in the aetiology of CML and Ph positive acute leukaemia . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
To investigate the clinicopathological role of bcr / abl in Ph 1 positive chronic myelogenous leukaemia ( CML ) , we studied the clonal origin of haematopoietic progenitors by detecting bcr / abl mRNA in a single haematopoietic colony using the polymerase chain reaction ( PCR ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The rearrangement within M BCR and ABL was detected in all patients including nine Ph positive CML , and three Ph negative CML . ^^^ The rearranged 3 ' abl fragments showed comigration with rearranged 5 ' bcr fragment in rare cutting restriction enzyme digests in all patients with Ph positive CML . ^^^ Meanwhile , the rearranged 3 ' bcr fragments showed comigration with rearranged pHabl 5 ' ( or T 39 1 2 ) fragments in all patients with Ph positive CML , indicating the linkage of the 5 ' end of ABL to the 3 ' part of M BCR on 9q+ chromosome . ^^^ The results suggest that a genomic insertion of 3 ' ABL into M BCR in Ph negative CML occurs by a single cytogenetic event rather than a two translocation mechanism . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Thirty three patients with chronic myelogenous leukemia ( CML ) treated by allogeneic bone marrow transplantation ( BMT ) were evaluated for bcr / abl mRNA using the reverse transcriptase polymerase chain reaction ( RT PCR ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The first clear cut association of an oncogene with a specific cancer is the c abl translocation in chronic myelogenous leukemia and acute lymphocytic leukemia ; it has been observed in 90 % of CML cases examined . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Secondary clonogenic cells derived at week 1 , 5 , and 8 from long term bone marrow cultures ( LTBMCs ) initiated with primitive progenitors , which lack HLA DR antigens , exhibit neither the Philadelphia chromosome ( Ph 1 ) nor the corresponding bcr / abl mRNA characteristic of CML . ^^^ In contrast , clonogenic cells recovered at week 1 , 5 , and 8 from LTBMCs initiated with the CML HLA DR+ population contain Ph 1 and express bcr / abl mRNA . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In vitro amplification of the Bcr Abl cDNA has been widely used to assess for the presence of minimal residual disease in patients with chronic myelogenous leukaemia ( CML ) presenting with complete clinical and cytogenetic remission . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The prognostic significance of detecting minimal residual disease by polymerase chain reaction ( PCR ) amplification of bcr / abl mRNA transcripts was investigated in 27 bone marrow samples from 20 patients with Philadelphia chromosome ( Ph 1 ) positive chronic myelogenous leukaemia ( CML ) in complete cytogenetic remission following allogeneic bone marrow transplantation . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Twenty six patients with Philadelphia chromosome ( Ph 1 ) positive chronic myelogenous leukemia ( CML ) treated with IFN alpha were classified on the basis of the fusion pattern of BCR / ABL chimeric mRNA determined by a reverse transcriptase polymerase chain reaction ( RT PCR ) method . ^^^ These results suggest that the fusion pattern of BCR / ABL mRNA may affect the therapeutic response to IFN alpha and clinical outcome in CML patients . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
It is proposed that a Pl linked cell adhesion molecule ( CAM ) is deficient in CML as a consequence of the constitutive activation of ABL kinase whilst , in normal cells , CAMs attached in this manner are responsible for efficient adhesion to stroma and are regulated by growth factors . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Although rare cells expressing the bcr / abl fusion transcript can be detected by the polymerase chain reaction ( PCR ) in patient blood or marrow after allogeneic bone marrow transplant ( BMT ) for Philadelphia chromosome ( Ph+ ) positive chronic myelogenous leukemia ( CML ) , the prognostic significance of this finding is unknown . ^^^ Nested primer PCR was performed on patient blood and bone marrow samples to detect the presence of residual bcr / abl ( + ) cells in CML patients considered to be in clinical remission at the time of study . ^^^ These data indicate that among CML patients in apparent clinical remission after BMT , nested primer bcr / abl PCR can define subgroups with low , intermediate , and high risk of relapse . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
By using antisense oligomers the functional role of the c abl proto oncogene in the in vitro growth of bone marrow hematopoietic progenitors from normal subjects and patients with chronic myelogenous leukemia ( CML ) has been evaluated . ^^^ These findings ( 1 ) confirm previous observations showing a lineage specific requirement of c abl function in normal hematopoiesis , and ( 2 ) suggest that the residual c abl expression has a role in chronic phase CML hematopoiesis , as its inhibition impairs both myeloid and erythroid colony formation in vitro . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
These data show that murine CML can result from retroviral transfer of the bcr / abl gene into pluripotent hematopoietic stem cells , that infected clones repopulate poorly after adoptive transfer , and that these clones can give rise to acute leukemia , reflecting evolution to a phase resembling blast crisis in the human disease . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
It is possible that the hybrid bcr / abl gene plays an important role in the pathogenesis of CML by subverting the mechanism of homeostasis through the uncoordinated activation of cell growth stimulating and regulating factors . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
More recent reports have suggested that 5 abl can , however , cause a disease similar to CML . ^^^ We demonstrate here that 5 abl , when transduced in a helper virus containing system , causes disease similar to , but distinct from , the CML like syndrome induced by bcr abl . ^^^ Unlike animals with CML like disease resulting from bcr abl , the polymorphonuclear leukocytes from animals infected with a 5 abl construct do not contain the 5 abl provirus at a significant frequency . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Persistence of BCR / ABL transcripts after BMT for CML detected by PCR reflects a high risk of relapse . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The molecular basis of CML involves activation of a cellular proto oncogene ABL . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Co detection of chimeric bcr / abl ( target ) and beta actin ( control ) messenger RNA in individual CFU GM colonies derived from CML patients using the polymerase chain reaction . ^^^ In order to quantitate the magnitude of the normal and Philadelphia ( Ph ' ) chromosome positive ( + ) progenitor cells for various research and clinical settings / studies , we have applied the highly sensitive polymerase chain reaction ( PCR ) for examining the cells contained in individual hematopoietic colonies for chimeric bcr / abl mRNA , a specific molecular marker for chronic myelogenous leukemia ( CML ) . ^^^ Using this method , we have examined the colonies grown from three CML patients and found that 5 out of 5 , 9 out of 9 and 8 out of 9 colonies contained a bcr / abl transcript . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The polymerase chain reaction was used to evaluate minimum residual disease in chronic myelogenous leukaemia ( CML ) patients after bone marrow transplantation , by amplification of the transcript of the specific bcr / abl hybrid gene . ^^^ In 11 of 12 CML patients in clinical and cytogenetic remission the bcr / abl transcript was detected 3 months to 6 years after transplantation . ^^^ Thus , it appears that cells expressing the bcr / abl mRNA are not eradicated from the blood of CML patients in complete clinical remission even years after bone marrow transplantation . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We conclude that ( 1 ) rIFN alpha does not have a significant leukaemia specific effect on the progenitor cells detected in these assays , and ( 2 ) the sensitivity of CML GM CFC to rIFN alpha is independent of the type of BCR / ABL message present in the cells . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The polymerase chain reaction ( PCR ) is a powerful technique for the detection of the bcr / abl rearrangement in chronic myelogenous leukemia ( CML ) . ^^^ Using this protocol , we investigated 20 patients with CML along with six healthy individuals and two cell lines derived from patients with CML for the presence of the bcr / abl rearrangement . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Although the BCR ABL protein can be routinely detected in blood cells from blast crisis CML patients by assaying for its activated tyrosine kinase activity , detection of P 210 BCR ABL in early stage CML patients ( chronic phase ) has not yet been possible ( S . ^^^ A procedure involving Western blotting with an anti ABL monoclonal antibody was developed that allows detection of P 210 BCR ABL and P 145 ABL in cells from chronic phase and blast crisis CML patients , but as expected only P 145 ABL was found in normal white blood cells . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
But the consistency and regularity with which blast crisis occurs and the irregularity with which the factors which are ascribed to cause it ( e . g . additional chromosomal abnormalities , change in bcr / abl rearrangement , etc . occur , suggests that CML BC is not a stochastic process in the natural history of CML but is predetermined at the time of the first mutation in the stem cell . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The ABL and PHL genes fragments fuse together , creating a new hybrid gene which is transcribed into an 8 . 5 kilobase messenger RNA specific to CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Bone marrow cells from 37 patients with chronic myelogenous leukemia ( CML ) , who had the characteristic Philadelphia chromosome in their leukemic cells , were examined for ABL gene rearrangement by pulsed field gel electrophoresis . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We sought evidence of BCR / ABL transcripts in the peripheral blood of nine CML patients in complete clinical and cytogenetic remission after treatment by bone marrow transplantation ( BMT ) or interferon and in one patient who entered spontaneous remission . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The Philadelphia ( Ph 1 ) chromosome ( 22q ) , found in more than 90 % of patients with chronic myeloid leukemia ( CML ) , is one part of a reciprocal translocation , t ( 9 ; 22 ) ( q 34 ; q 11 ) , in which the oncogene c abl moves from 9q34 to 22q11 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
An altered c abl gene product ( P210bcr abl ) possessing associated tyrosine protein kinase activity was recently been reported in several blast chronic myelogenous leukemia ( CML ) cell lines . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
An aberrant p210BCR ABL protein that possesses constitutive protein tyrosine kinase activity is presumed to be involved in the development of the neoplastic phenotype in chronic myelogenous leukemia ( CML ) . ^^^ Using a highly specific antibody against phosphotyrosine , we have isolated the tyrosine phosphorylated p210BCR ABL and several other proteins containing phosphotyrosine from a variety of CML cell lines . p210BCR ABL isolated by the monoclonal anti phosphotyrosine antibody possessed protein tyrosine kinase activity in vitro comparable to that of the p210BCR ABL isolated by antibody to a specific peptide sequence in the ABL protein tyrosine kinase . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The CML specific P 210 bcr / abl protein , unlike 5 abl , does not transform NIH / 3T3 fibroblasts . ^^^ The role of its relative , the bcr / abl gene product , in the etiology of human chronic myelogenous leukemia ( CML ) remains speculative . ^^^ To assess the transforming properties of the bcr / abl gene product , complementary DNA clones encoding the CML specific P 210 bcr / abl protein were expressed in NIH / 3T3 fibroblasts . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Here we show that P 210 bcr / abl protein expression varies greatly in different Ph 1 chromosome positive B lymphoid cell lines obtained from Epstein Barr virus transformed lymphocytes of a CML patient in the chronic phase . ^^^ An altered c abl protein ( P 210 ) bearing increased tyrosine kinase activity represents the product of the hybrid bcr / c abl gene arising as a consequence of the Philadelphia ( Ph 1 ) chromosome translocation , the consistent cytogenetic abnormality of chronic myelogenous leukemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We discuss the basic aspects of differential diagnosis between T lymphoblastic lymphoma with leukemoid reaction and T lymphoid lymphadenopathic blastic crisis of Ph negative , bcr / abl negative CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Interstitial insertion of varying amounts of ABL containing genetic material into chromosome 22 in Ph negative CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The c abl locus is translocated from chromosome 9 to chromosome 22 in chronic myelogenous leukemia ( CML ) , creating the Philadelphia chromosome ( 22q , Ph 1 ) , one of the most consistent chromosomal abnormalities found in human hematologic malignancy . ^^^ We have isolated cloned human c abl probes to analyze the organization and expression of abl genes in patients with CML and in K 562 cells . ^^^ These results provide evidence that the c abl locus is abnormally expressed in CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chromosome in situ hybridization showed that the ABL oncogene was translocated from chromosome 9 to chromosome 22 in the CML patients but remained on chromosome 9 in the AML patients . ^^^ These results indicate that the breakpoint at 9q34 in CML is 5 ' of ABL , whereas the breakpoint at 9q34 in AML is 3 ' of ABL . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Abnormalities in structure and expression of the proto oncogene c abl have been implicated in the genesis of chronic myelogenous leukemia ( CML ) . ^^^ We studied leukemic cell DNA from 42 CML patients for evidence of rearrangement and / or amplification of c abl analogous to that described in the CML cell line K 562 . ^^^ Thus , amplification of c abl and loss of one c abl allele are both infrequent in CML and do not play a significant role in the course of the disease . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The translocation of the abl oncogene to the Philadelphia chromosome in chronic myelogenous leukemia ( CML ) results in a new RNA transcript that fuses sequence from chromosome 22 to sequence from the abl oncogene . ^^^ This RNA presumably codes for a new abl related protein product found in CML , the activity of which is different from the normal abl protein . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Amplification of rearranged c abl oncogenes in CML blast crisis . ^^^ Several patients with CML blast crisis exhibiting multiple Ph 1 chromosomes / metaphase exhibited amplified and rearranged c abl related fragments . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The new fusion gene , with chromosome 22 sequence at its 5 ' end and chromosome 9 abl sequence at its 3 ' end , generates a new messenger RNA ( mRNA ) and protein that are implicated in the pathogenesis of CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The abl gene and CML serve as a paradigm of the mechanism of activation of proto oncogenes by chromosomal alterations . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
CML cells carrying the t ( 9 ; 22 ) chromosomal translocation are known to produce an 8 kilobase ( kb ) c abl transcript in addition to the normal 6 and 7 kb transcripts and to express the normal p 145 abl protein and a p 210 c abl protein possessing a tyrosine kinase activity not detected in the p 145 species . ^^^ Results of our analyses using somatic cell hybrids between a mouse fibroblast line and two human CML derived cell lines which carry the Ph 1 chromosome and are phenotypically identical to the fibroblast parent indicate that only the hybrid cells containing Ph 1 chromosome express both the 8 kb c abl RNA and the p 210 protein . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Human chronic myeloid leukemia ( CML ) cells and cell lines have been shown to contain an active bcr c abl p 210 tyrosine kinase as a consequence of the Philadelphia chromosomal translocation . ^^^ In the present work the activity of the c abl and c src oncogene encoded tyrosine kinase was investigated during phorbol diester ( TPA ) induced differentiation of the K 562 CML cells . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
This confirms the hypothesis that the translocation of c abl oncogene is essential for the development of Ph 1 positive CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The most common karyotypic change that occurs as CML evolves from chronic phase to blast crisis is the development of multiple Philadelphia ( Ph 1 ) chromosomes , each of which is presumably harboring a translocated c abl oncogene . ^^^ We describe here a patient with CML who presented in lymphoid blast crisis with three Ph 1 chromosomes / metaphase associated with an amplified , rearranged c abl oncogene fragment and high levels of the aberrant 8 kilobase bcr abl transcript . ^^^ This rearranged c abl fragment was amplified to a similar degree in both the patient ' s blast crisis cells and in his terminally differentiated granulocytes , but the level of the aberrant CML specific bcr abl transcript was some eight to 16 fold higher in the blast crisis cells 5 the granulocytes . ^^^ This analysis indicates that genomic amplification of a translocated c abl oncogene , although perhaps important in the evolution of CML , nevertheless can not , by itself , be the sole genetic event giving rise to blast crisis . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Although the importance of c sis and c abl oncogenes is gaining popularity yet their role in the genesis of CML remain obscure . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Over 90 % of chronic myelogenous leukemia ( CML ) is characterized by a reciprocal translocation that brings c abl from chromosome 9 to chromosome 22 , and c sis from chromosome 22 to chromosome 9 . ^^^ All of the CML Philadelphia chromosome positive ( Ph1+ ) samples expressed an aberrant 8 kb c abl transcript . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Isochromosome 1 ( 22q ) confirmed by in situ hybridization of 5 abl gene in a case of CML in blast crisis ] . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We demonstrate that an aberrant 8 Kb c abl related transcript is present in the RNA of the leukemic cell from all patients with Ph+ CML and that the loss of both normal chromosome # 9 is associated with the loss of the normal c abl related transcripts . ^^^ This represents direct evidence that the normal c abl related transcripts derive from the normal c abl gene locus on the normal chromosome # 9 , while the aberrant c abl related transcript in Ph+ CML derives from the hybrid bcr abl gene formed as a result of the t ( 9 ; 22 ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The Philadelphia chromosome ( Ph 1 ) , observed in greater than 90 % of chronic myelogenous leukemia ( CML ) patients , results from a specific chromosomal translocation involving the c abl gene . ^^^ In the CML derived cell line K 562 , Ph 1 is accompanied by a structurally altered c abl protein ( P210c abl ) with in vitro tyrosine kinase activity not detected with the normal c abl protein ( P145c abl ) . ^^^ We have examined c abl proteins in other Ph 1 positive CML cell lines and found that they all express P210c abl . ^^^ Based on these results we propose that translocation of c abl in Ph 1 positive CML results in the creation of a chimeric gene leading to the production of a structurally altered c abl protein with activated tyrosine kinase activity . ^^^ The altered P 210 c abl protein is strongly implicated in the pathogenesis of CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In two patients with chronic myeloid leukemia ( CML ) , the nature of the chromosomal rearrangement giving rise to `` masked ' ' Ph has been studied by in situ hybridization of human c abl sequences . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The finding of this rare 22 translocation in classical CML would seem to support the hypothesis that the crucial event in the pathogenesis of CML is the translocation of band 9q34 , that contains the c abl oncogene , onto the Ph ' chromosome , rather than the translocation of the tract deleted from 22 to some other chromosome site . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Molecular analysis of the Philadelphia translocation in leukemic cells of CML patients revealed a consistent translocation of the human c abl oncogene from chromosome 9 to the Ph 1 chromosome , regardless of the cytogenetic subtype . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Moreover , abl was shown to be translocated from chromosome 9 to 22 and sis from chromosome 22 to 9 in CML patients with t ( 9 ; 22 ) . ^^^ We analyzed expression of the abl and sis oncogenes in leukemic cells from CML patients with t ( 9 ; 22 ) . ^^^ This abl RNA is also present in two leukemic cell lines ( EM 2 and K 562 ) , which were derived from CML patients and contain the t ( 9 ; 22 ) . ^^^ The consistent presence of this abl RNA transcript in CML with t ( 9 ; 22 ) suggests that it is a consequence of abl translocation and that it plays a role in the development of this leukemia . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Leukaemic cells from 5 of 6 patients with chronic myelogenous leukaemia ( CML ) and the Ph 1 chromosome were found to contain a new 8 kb abl RNA transcript . ^^^ This finding raises the possibility that the abl oncogene is directly involved in the development of CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Recently , we localized the human c abl oncogene to chromosome region 9q34 and demonstrated a translocation of this gene to the Philadelphia chromosome ( Ph 1 , 22q ) in various forms of Ph 1 positive , but not Ph 1 negative , chronic myelocytic leukemia ( CML ) . ^^^ Thus , if either of these two oncogenes is involved in the development of Ph 1 positive CML , c abl appears to be the more important one . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Two notable examples are that of the t ( 9 ; 22 ) translocation of chronic myelogenous leukemia ( CML ) , causing the transfer of the oncogene c abl from chromosome 9 to chromosome 22 , and that of the t ( 8 ; 14 ) translocation of Burkitt lymphoma , causing the transfer of the oncogene c myc from chromosome 8 to chromosome 14 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
It was recently suggested that the translocation of the c abl gene ( the human cellular homologue of the transforming sequence of Abelson murine leukaemia virus ) from chromosome 9 to 22 in Philadelphia translocation , might have a role in the generation of chronic myeloid leukaemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Expression of the cellular abl ( c abl ) oncogene was studied in K 562 and other chronic myelogenous leukemia ( CML ) cells and cell lines by means of Northern blot hybridization . ^^^ In contrast to non CML cells , which contained 7 . 4 and 6 . 8 kilobase abl related transcripts , the CML cells contained a predominant and novel 8 . 2 kilobase abl related RNA . ^^^ In addition , the levels of abl related message were up to eight times higher in CML cell lines from patients at the blast crisis stage of the disease compared with CML cells obtained during the chronic phase and with non CML cells . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
From this we conclude that in CML , c abl sequences are translocated from chromosome 9 to chromosome 22q . ^^^ This finding is a direct demonstration of a reciprocal exchange between the two chromosomes and suggests a role for the c abl gene in the generation of CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The Philadelphia chromosome translocation generates a chimeric oncogene , BCR / ABL , which causes chronic myelogenous leukemia ( CML ) . ^^^ Anti CRKL immunoprecipitates from CML cells , but not normal cells , were found to contain p210BCR / ABL and c ABL . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We compared the results of cytogenetic analysis and double color FISH detection of bcr / abl genes fusion in 13 CML patients on IFN alpha therapy ( marrow sampling for cytogenetic and FISH analysis was carried out after 12 months in all patients and repeated after 18 months of IFN therapy in patients 4 , 6 , and 8 ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The dual color FISH technique , performed using specific painting probes for chromosomes 9 , 21 , 22 and a BCR / ABL translocation probe , enabled us to confirm the diagnosis of CML by detecting the BCR / ABL rearrangement on chromosome 22q and the involvement of chromosome 9 in a variant translocation t ( 9 ; 21 ; 22 ) . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
An aberrantly expressed and highly active abl tyrosine kinase ( p210bcr abl ) appears critical for the development and pathogenesis of chronic myelogenous leukemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Although the break in CML chromosomes at 9q34 and the location of c abl at 9q34 could be unrelated , it seems more likely that the two genetic events are associated with evolution of malignant hematopoiesis of man . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Forty CML patients , Philadelphia positive or with BCR / ABL rearrangement , were studied at diagnosis . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In Philadelphia ( Ph ) positive chronic myeloid leukemia ( CML ) the BCR / ABL fusion genes can be transcribed in at least two different mRNAs that can either include ( a2b3 ) or exclude ( a2b2 ) the exon 3 of the major breakpoint cluster region in chromosome 22 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Binding of BCR / ABL junctional peptides to major histocompatibility complex ( MHC ) class 1 B 35 molecules : relationship between antigen defective cell lines and HLA frequencies in CML patients . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
It has been suggested that the breakpoint location within the M BCR segment of chromosome 22 and the type of chimeric mRNA BCR / ABL ( b2a2 or b3a2 ) are associated with differences in the clinical and hematological characteristics of chronic myelogenous leukemia ( CML ) . ^^^ To assist in clarifying this matter , in a series of Ph positive CML patients the relationship of both the breakpoint location within M BCR ( n = 71 ) and the type of chimeric mRNA BCR / ABL ( n = 40 ) with the chronic phase duration , patients ' survival , and thrombopoietic activity was analyzed . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
There is some degree of consensus that the mechanism by which IFN alpha suppresses the Ph+ clone in CML consists in the restoration of normal adhesion of CML progenitors to the marrow stroma , by preventing transcription of the BCR / ABL mRNA , and hence expression of the p 210 tyrosine kinase . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Previous experiments have shown that CRKL is phosphorylated on tyrosine in the chronic myelogenous leukemia ( CML ) cell line K 562 and that CRKL is a substrate for ABL and for BCR / ABL in COS 1 cells . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Stimulation of normal neutrophils with cytokines and agonists did not induce tyrosine phosphorylation of proteins migrating in the region of pp 39 , and the phosphorylation state of pp 39 in CML neutrophils was not affected by kinase inhibitors known to downregulate the ABL kinase . ^^^ Our results suggest that pp 39 CRKL in CML neutrophils may be stably tyrosine phosphorylated by the BCR / ABL kinase at an early stage of myeloid differentiation when the ABL kinase is active . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We used reverse transcription polymerase chain reaction ( RT PCR ) to investigate expression of the BCR / ABL transcript of individual hematopoietic progenitors from a CML patient in blastic phase . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Long term culture of marrow from patients with chronic myelogenous leukemia ( CML ) has been reported to favor the outgrowth of bcr / abl progenitor cells in some patients . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The presence of genetic markers , such as the BCR / ABL rearrangement in chronic myelogenous leukemia ( CML ) , has allowed highly sensitive detection of residual leukemic cells by polymerase chain reaction ( PCR ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Fluorescence in situ hybridization ( FISH ) using chromosome specific DNA libraries in conjunction with a cosmid probe for the c ABL oncogene was performed to substantiate the preliminary G banded karyotypes of six patients with chronic myelogenous leukemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Polymerase chain reaction analysis of RNA samples from these CD34+ subpopulations was used to detect the presence of the BCR / ABL translocation characteristic of CML . ^^^ The CD34+DR+ subpopulation contained BCR / ABL ( + ) cells in 11 of 12 marrow samples studied , whereas the CD34+DR subpopulation contained BCR / ABL ( + ) cells in 6 of 9 CML marrow specimens . ^^^ These CD34+ cells were also used to establish stromal cell free long term bone marrow cultures to assess the BCR / ABL status of hematopoietic stem cells within these CML marrow populations . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The translocation in CML gives rise to two BCR / ABL chimeric transcripts ( b3a2 and b2a2 ) encoding a 210 kD tyrosine kinase protein . ^^^ With PCR , we looked for BCR / ABL transcripts in 30 patients with CML and 4 with essential thrombocythaemia at time of diagnosis , finding a significant difference in the platelet counts of CML patients carrying b3a2 or b2a2 transcripts . ^^^ The BCR / ABL transcript was monitored by PCR in 6 CML patients after BMT . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Two hundred and nineteen cases of Ph+ve CML and 15 Ph ve , BCR+ve CML cases have been analysed to determine the breakpoint site and its relationship to clinical features , cytogenetic response , duration of chronic phase and survival . 119 cases have had RNA analysis performed to determine the type of BCR / ABL transcript and have also been analysed in a similar way . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
These results suggest that B2A2 AS may be cross reactive with B3A2 AS on the growth suppression of CML cells under certain culture conditions , possibly due to their partial hybridization to the ABL portion of the target mRNA , although other non sequence specific mechanisms are also possible . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The use of specific ODNs or antisense constructs to downregulate p 85 alpha expression showed a requirement for p 85 alpha subunit in the proliferation of BCR / ABL dependent cell lines and chronic myelogenous leukemia ( CML ) primary cells . ^^^ Thus , PI 3 kinase is one of the downstream effectors of BCR / ABL tyrosine kinase in CML cells . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Simultaneous monitoring of MRD by RT PCR using primers for specific DNA markers in four patients ( two AML M 3 with PML / RAR alpha , one AML M 2 with AML1 / ETO , and one CML with bcr / abl ) detected MRD comparable to that obtained from quantitation of WT 1 gene expression . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BCR / ABL in CML , PML / RAR alfa in APL , AML1 / ETO in t ( 8 ; 21 ) AML and CBFB / MYH1 in inv ( 16 ) AML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Philadelphia chromosome ( Ph ) positive K 562 cells possess multiple copies of the bcr / abl fusion gene whose transcript and protein product ( p 210 ) is thought to confer growth advantage to CML cells . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Interferon alpha 2a therapy in CML : disappearance of BCR / ABL transcript in a case of long lasting continuous cytogenetic conversion . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Recent studies suggest that the BCR ABL gene plays a critical role in the pathogenesis of Ph+ chronic myeloid leukemia ( CML ) . ^^^ We investigated the hematopoietic colonies derived from the marrows of 12 patients with Ph+ CML in chronic phase by reverse transcriptase polymerase chain reaction ( RT PCR ) amplification of BCR ABL mRNA and by cytogenetics . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
This observation suggests that in at least some CML patients drug therapy can suppress or eliminate an aggressive malignant cell clone , but that the underlying molecular defect in haemopoietic cells ( in this case the c ABL translocation ) persists and other aggressive clones with different molecular lesions eventually arise . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Therefore , we examined the effect of c Myc protein downregulation , using antisense oligodeoxynucleotides , on the growth of the BCR / ABL dependent cell line and chronic myelogenous leukemia ( CML ) patients cells . ^^^ Downregulation of c Myc expression caused complete inhibition of the proliferation of BCR / ABL dependent BV 173 cell line and 50 70 % inhibition of the colony formation of CML cells . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We can further speculate that the loss of p 53 function , at the time of blastic crisis of CML , may play a role , in combination with other genetic changes ( p 210 BCR / ABL , Rb gene abnormality , others to be defined ) , in inducing disturbances in cell proliferation , differentiation , and apoptosis . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The CML cell lines tested showed different sensitivities to inhibition of proliferation by AOs lines with defective expression of the normal ABL protooncogene ( e . g . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The Philadelphia translocation commonly observed in chronic myeloid leukaemia ( CML ) and a proportion of cases of acute leukaemia results in the creation of a chimeric fusion protein , BCR ABL . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Detection of the chronic myelogenous leukemia ( CML ) related marker , the bcr / abl m RNA transcript , in blood or bone marrow of patients with CML in hematologic remission after allogeneic bone marrow transplantation ( allo BMT ) may be associated with the presence of minimal residual disease but does not uniformly predict hematologic relapse . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The Philadelphia chromosome ( Ph 1 ) , present in > or = 95 % of chronic myelogenous leukemia ( CML ) patients , is a well characterized translocation that results in a unique chimeric gene product ( BCR / ABL ) with transforming capability . ^^^ Molecular methods utilizing the polymerase chain reaction ( PCR ) to detect BCR / ABL mRNA transcripts has been useful for detecting minimal residual disease ( MRD ) after treatment , as well as for establishing the diagnosis of CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The Philadelphia chromosome ( Ph 1 ) , detected in virtually all cases of chronic myelogenous leukemia ( CML ) , is formed by a reciprocal translocation between chromosome 9 and 22 that fuses Bcr encoded sequences upstream of exon 2 of c Abl . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In patients with chronic myelogenous leukaemia ( CML ) treated by allogeneic bone marrow transplantation ( BMT ) , detection of residual leukaemic cells carrying the characteristic bcr / abl rearrangement by highly sensitive techniques , such as qualitative polymerase chain reaction ( PCR ) , is of limited value in predicting disease progression . ^^^ We have therefore adapted the PCR for quantitative assessment of bcr / abl rearranged cells and applied this technique to the monitoring of residual disease in 28 CML patients during up to 106 months of follow up after BMT . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In addition , in patients with CML karyotyping and analysis of bcr / abl gene rearrangement was performed . ^^^ Simultaneous analysis of chimerism after BMT by VNTR RFLP , karyotyping , and detection of bcr / abl rearrangement in patients with CML showed corresponding results in nine out of 12 patients . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Ph+ chronic myelogenous leukemia ( CML ) is associated with the reciprocal translocation between chromosomes 9 and 22 culminating in the production of the chimeric p210bcr / abl protein possessing elevated protein tyrosine kinase activity relative to the normal c abl tyrosine kinase . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In the first year following BMT for CML , PCR used to detect the leukemia specific BCR / ABL message frequently reveals subclinical levels of persisting leukemia . ^^^ Furthermore , studies of the association of GVHD with PCR detection of BCR / ABL message may shed light on the relationship of GVL with minimal residual disease in CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
One of these genes , the fusion gene BCR / ABL resulting from the balanced translocation ( 9 ; 22 ) has received wide attention owing to its intimate involvement in CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BCR ABL fusion constructs encoding an 185 kDa protein as in acute leukemia , or a 210 kDa protein as in chronic myelocytic leukemia ( CML ) , did not accelerate pristane induced PC development in the N myc transgenic mice , in contrast to their known ability to immortalize lymphoid cells in vitro . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The role of abl gene expression in normal and chronic myelogenous leukemia ( CML ) cells is not yet completely understood . ^^^ Selective inhibition of this proto oncogene and of the abl bcr oncogene have been achieved by using of c abl sequence specific antisense oligonucleotides ; this approach sheds new light on the function of this gene in CML . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In CML , the product of the fused BCR ABL gene is typically a protein of approximately 2 , 000 amino acids termed P 210 BCR ABL . ^^^ This assay was used to analyze the BCR ABL protein content of circulating WBC from CML patients before and after various treatments . ^^^ Of interest , six Ph 1 negative CML patients were BCR ABL protein positive . ^^^ Our results indicate that the BCR ABL Western blotting assay has clinical applications for both diagnosis and prospective evaluation of Ph 1 positive and Ph 1 negative CML patients . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
CML originates in a multipotential stem cell due to its acquiring a highly consistent specific chromosomal translocation between chromosomes 9 and 22 ; this results in a fused bcr / abl gene and an abnormal 210 kDa fusion protein which has increased intrinsic protein tyrosine kinase activity compared to the normal c abl protein . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The aim of this study was to analyze the usefulness of bcr / abl rearrangement in the diagnosis and evolution of chronic myeloid leukemia ( CML ) . ^^^ METHODS : The rearrangement of the bcr / abl gene was studied in 81 cases of which 34 corresponded to patients with CML ( 29 Ph ' positive chromosome , 2 Ph ' negative chromosome and 3 without karyotype ) , 2 patients with Ph ' positive acute lymphoblastic leukemia , 15 patients with chronic myeloproliferative syndromes different from CML and 30 controls . ^^^ RESULTS : Rearrangement of the bcr / abl gene was observed in all the patients with CML except in one with Ph ' negative chromosome . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We have investigated the involvement of tumor suppressor genes ( p 53 and RB 1 ) and dominantly acting oncogenes ( Ras family genes ) in BCR / ABL positive and negative chronic myeloproliferative disorders ( CMPD ) at different stages of the disease , including 26 cases of BCR / ABL+ chronic myeloid leukemia ( CML ) blast crisis , 9 myelosclerosis with myeloid metaplasia , 4 polycythemia vera , 10 essential thrombocythemia , 1 juvenile CML , and 8 BCR / ABL CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In the absence of various clinical influences that can modulate NAP activity in chronic phase CML , the results reinforce the observation that the BCR / ABL fusion gene product is not a key factor influencing NAP activity in CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
No amplification of c abl or c myb oncogenes was detected in the DNAs of Ph negative CML cells . ^^^ Data suggest that co operation between the overexpressed c abl and c myb oncogenes is causally related to Ph negative bcr negative CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We report that transient expression of p210bcr / abl in fibroblast like cells induces simultaneous activation of p21ras and inhibition of GTPase promoting activity of p120GAP , and confirm these data showing that downregulation of p210bcr / abl expression in CML cells with bcr / abl antisense oligodeoxynucleotides induces both inhibition of p21ras activation and stimulation of GTPase promoting activity of p120GAP . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic myelogenous leukemia ( CML ) is characterized by a specific chromosomal translocation occurring between the long arms of chromosomes 9 and 22 resulting in a fusion product , p 210 BCR / ABL , which has elevated tyrosine kinase activity . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The t ( 9 , 22 ) chromosomal translocation generating the Philadelphia chromosome and the BCRABL oncogene has been shown both cytogenetically and molecularly to be the etiologic event in chronic myelogenous leukemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Role of c abl oncogene in chronic myeloid leukemia ( CML ) , bcl 2 , in lymphomas , N myc in neuroblastomas and retinoblastoma ( Rb ) gene in retinoblastomas is well understood and used in designing proper therapeutic approaches . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Parts of the Bcr / Abl hybrid transcript supposed to be important for its transforming ability were sequenced in a series of CML blast crises , in order to evaluate the possible presence of alterations responsible for the disease transition from the chronic to the acute phase . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The use of BCR / ABL to recreate CML in mice fulfills Koch ' s postulates for molecular pathogenesis . ^^^ The present murine systems facilitate research into the biology of BCR / ABL induced leukemias , but fall short in their promise to provide models for testing new therapies for CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Six of the eight patients with stable CML after relapse had complete remissions according to molecular genetic criteria , since no cells with bcr / abl messenger RNA transcripts were detected ( the method can identify 1 leukemic cell among 1 million normal cells ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Recent developments in the understanding of the process of antigen presentation by major histocompatibility complex ( MHC ) molecules and their recognition by T lymphocytes has led investigators to speculate that the hybrid bcr / abl fusion protein P 210 present in chronic myeloid leukemia ( CML ) cells may generate leukemia specific antigens recognized by T cells . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
For the five CML samples tested to date , the majority of CFU A colonies at diagnosis or in early chronic phase were found to be bcr / abl positive . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In chronic myelogenous leukemia ( CML ) the reciprocal translocation of the long arms of chromosomes results in the formation of the unique BCR / ABL fusion gene which is believed to play a crucial role in the pathogenesis of CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In this study , we showed the detecting for MRD by molecular biology techniques in the patients with non Hodgkin ' s lymphoma , CML , B ALL and AML . 1 ) Malignant cells could be detected in peripheral blood or bone marrow cells by Southern blot analysis in 15 of 30 patients with non Hodgkin ' s lymphoma . 2 ) In CML patients , BCR / ABL fusion gene was positive by RT PCR for 6 months after BMT , 4 patients became undetectable for 7 months after BMT . 3 ) Rearrangement of Ig H has been disappeared in 12 months after achieved complete remission the patients with B ALL . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chromosomal deletions of band 13q14 occur recurrently in BCR / ABL negative chronic myeloproliferative disorders ( CMPD ) , including myelosclerosis with myeloid metaplasia ( MMM ) , polycythemia vera ( PV ) , essential thrombocythemia ( ET ) , juvenile chronic myeloid leukemia ( JCML ) , and the so called BCR / ABL chronic myeloid leukemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Despite the high level of T cell reactivity to autologous tumor cells in short term ( 6 days ) culture , 1 ) they failed to respond to synthetic peptides corresponding to the bcr / abl fusion sequence of the patient , and 2 ) only one proliferative T cell clone ( TCC ) was isolated which specifically recognized HLA DR matched CML cells . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The detection of the t ( 9 ; 22 ) translocation , typical of chronic myeloid leukaemia ( CML ) , can be accomplished by cytogenetical detection of Philadelphia ( Ph 1 ) chromosome or by molecular analysis of the bcr / abl fusion gene with nucleic acid probes after amplification by polymerase chain reaction ( PCR ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Rearrangements of the c abl protooncogene and the bcr gene are found in > 90 % of patients in chronic phase of chronic myelogenous leukemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
ZNF 79 mapped to 9q34 centromeric to the ABL gene and between a constitutional chromosomal translocation on the centromeric side and the CML specific ABL translocation on the telomeric side . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
To evaluate the remission quality of Philadelphia chromosome ( Ph ) positive , BCR / ABL positive CML patients after allogeneic bone marrow transplantation ( BMT ) we used the polymerase chain reaction ( PCR ) to detect BCR ABL specific RNA in addition to Southern blotting , cytogenetic , and hematological investigation . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
CML is defined as a myeloproliferative disorder with molecular or cytogenetic evidence of the translocation of the abl oncogene on chromosome 9 to the break point cluster region gene on chromosome 22 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The BCR / ABL mRNA , which is specific for CML , was detected in the blastic cells by a method using reverse transcriptase and polymerase chain reaction . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The Philadelphia ( Ph ) translocation [ t ( 9 ; 22 ) ( q 34 ; q 11 ) ] is the most common genetic abnormality in human leukemia ; a transposition of the ABL gene to the major breakpoint cluster region ( M BCR ) is associated with the pathogenesis in Ph+ chronic myelogenous leukemia ( Ph+ CML ) and in some cases of Ph+ acute leukemia ( Ph+ AL ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The polymerase chain reaction ( PCR ) was used to amplify the bcr / abl transcript as a marker of minimal residual disease ( MRD ) in 76 patients with chronic myeloid leukemia ( CML ) subjected to allogeneic BMT and in complete hematological remission . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In chronic myelogenous leukemia ( CML ) , the Philadelphia ( Ph ) chromosome translocation results in the formation of BCR / ABL genes , normally transcribed in two types of hybrid transcripts with a b2a2 or b3a2 BCR / ABL junction , which give origin to 210 kD fusion proteins ( P 210 ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Variable numbers of BCR ABL transcripts persist in CML patients who achieve complete cytogenetic remission with interferon alpha . ^^^ A substantial minority of patients with chronic myeloid leukaemia ( CML ) achieve a complete response to treatment with interferon alpha ( IFN alpha ) , defined as the disappearance of Philadelphia chromosome positive metaphases or , for patients who are Philadelphia chromosome negative but BCR ABL positive , the disappearance of the leukaemic clone as assayed by Southern blot . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We sought to establish the relationship between BCR ABL transcript numbers measured by competitive 2 step reverse transcription polymerase chain reaction ( RT PCR ) and cytogenetic status in CML patients treated with IFN alpha . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Patients were monitored for response of leukemia , including in CML , the use of the polymerase chain reaction for bcr / abl mRNA transcripts and for the occurrence of graft versus host disease ( GVHD ) and myelosuppression . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We have examined the effect of BCR / ABL junctional antisense phosphodiester oligodeoxyribonucleotides ( ODNs ) on BV 173 and other chronic myeloid leukemia ( CML ) cell lines . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
To determine if CPT is able to exert selective antileukemic effect , 1 : 1 mixture of NBMC and CML BC cells was exposed to CPT in the absence of growth factors and assayed for growth ability in clonogenic assay and for expression of BCR / ABL transcript in single colonies . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The bcr abl oncogene , present in 95 % of patients with chronic myelogenous leukemia ( CML ) , has been implicated as the cause of this disease . ^^^ In colony forming assays of peripheral blood or bone marrow from patients with CML , there was a 92 98 % decrease in the number of bcr abl colonies formed but no inhibition of normal colony formation . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Characteristic of Philadelphia ( Ph ) + chronic myelogenous leukemia ( CML ) is the presence of the chimeric BCR / ABL ( p 210 ) protein possessing elevated protein tyrosine kinase activity relative to the normal c abl tyrosine kinase . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We have previously reported that selection of marrow cells on the basis of the CD34+HLA DR phenotype ( 34+DR ) may result in the recovery of Philadelphia chromosome ( Ph ) and BCR / ABL negative long term culture initiating cells ( LTC IC ) in selected patients with chronic myelogenous leukemia ( CML ) . ^^^ Furthermore , 34+DR cells from more than 80 % of ECP CML patients were BCR / ABL mRNA and Ph negative and contained only BCR / ABL mRNA and Ph negative LTC IC , whereas 34+DR cells and LTC IC from less than 40 % of AP CML patients were BCR / ABL mRNA and Ph negative . ^^^ CML 34+DR+ cells and LTC IC were BCR / ABL mRNA and Ph positive . ^^^ Thus , large scale selection of a BCR / ABL mRNA and Ph negative 34+DR cell population is possible in a fraction of chronic phase CML patients , in whom these cells could be used to reconstitute the hematopoietic compartment following autologous transplantation . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We found that the NPCF isolated from the nuclei of leukocytes of normal individuals rarely contained detectable quantities of tightly bound c abl , p 53 or blc 2 genes or gene sequences , whereas in CML nuclei these genes were often found in tight association with multiple NPCF . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The formation of the unique fusion gene , bcr abl , and the resultant increase in abl tyrosine kinase activity , is seen as the major driving force in the initiation of chronic myelogenous leukaemia ( CML ) . ^^^ Thus the large increase In mature myeloid cells seen in CML could be the direct result of the suppression of apoptosis by the bcr abl fusion protein . ^^^ The role and contribution of apoptosis in the progression of CML and the possible role of antisense oligonucleotides to the bcr abl gene as therapeutic agents is discussed . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
High levels of hLH 2 expression were observed in all cases of chronic myelogenous leukaemia ( CML ) tested , regardless of disease status . hLH 2 was mapped to chromosome 9Q33 34 . 1 , in the same region as the reciprocal translocation that creates the BCR ABL chimera of the Philadelphia chromosome ( Ph ' ) , the hallmark of CML ; hLH 2 was retained on the derivative 9 chromosome and is therefore centromeric of c ABL . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Furthermore , all 36 EBV induced lymphoblastoid cell lines established from six chronic phase CML patients showed unequivocal LH 2 expression , regardless of the BCR ABL status of the line ( 9 BCR ABL positive , 27 BCR ABL negative ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We investigated the persistence of host type hematopoiesis as defined by mixed chimerism ( MC ) in 28 male patients with chronic myelogenous leukemia ( CML ) who underwent opposite sex , non T cell depleted bone marrow transplantation ( BMT ) by amplification of Y chromosome specific sequences , and correlated these results with the detection of minimal residual disease ( MRD ) by BCR / ABL mRNA amplification . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The chimaeric bcr / abl oncogene is detected in virtually all cases of chronic myelogenous leukaemia ( CML ) . ^^^ Finally , colony assays with bone marrow from bcr / abl positive CML patients showed that the haemopoietic progenitors of three of four patients did not respond to rhSF . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We sought to establish the relationship between BCR ABL transcript numbers measured by competitive two step reverse transcription polymerase chain reaction ( RT PCR ) and cytogenetic status in CML patients treated with IFN alpha . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The RT PCR used in the present study for detection of the major bcr abl fusion gene , the hallmark and presumably the cause of CML , was optimized by : ( a ) increasing the amount of total RNA involved in the reverse transcription reaction to correspond to total RNA extracted from 10 ( 8 ) cells ; ( b ) using a specific abl primer in this reverse transcriptase reaction , and ( c ) reamplifying 10 % of the RT PCR product in a nested amplification . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic myelogenous leukemia ( CML ) is characterized by the t ( 9 ; 22 ) translocation that results in chimeric genes encoding bcr / abl fusion proteins . ^^^ We investigate here the binding of synthetic bcr / abl peptides to various HLA DR alleles and their recognition by T cells from normal donors and CML patients . ^^^ T cells recognizing bcr / abl peptides were not identified in any of the CML patients studied , regardless of HLA type . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The authors analyzed 1 , 155 peripheral blood samples from CML patients , for which there were same day Ph data , to determine if there was a correlation between bcr abl protein levels and the percentage of Ph . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We also assessed minimal residual disease using detection of the chimeric BCR / ABL transcripts by PCR of CML patients in this study . ^^^ In four of 14 ( 29 % ) patients who underwent PBPCT , the BCR / ABL chimeric transcript was detected , while after BMT eight of 14 ( 57 % ) CML patients remained BCR / ABL positive . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic myelogenous leukemia ( CML ) is a clonal disorder of the hematopoietic stem cell characterized by a chimeric BCR / ABL gene giving rise to a 210 kD fusion protein with dysregulated tyrosine kinase activity . ^^^ Analysis of individual CML colonies for the presence of the hybrid BCR / ABL mRNA by reverse transcription polymerase chain reaction ( RT PCR ) showed that genistein treatment significantly reduced the mean + / SD percentage of marrow BCR / ABL+ progenitors both by continuous exposure ( 76 % + / 18 % 5 24 % + / 12 % , P < or = . 004 ) or preincubation ( 75 % + / 16 % 5 21 % + / 10 % , P < or = . 002 ) experiments . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In contrast to the human chronic myeloid leukemia ( CML ) associated BCR / ABL fusion transcript , where a strong bias was claimed that was attributed to imprinting , we have found that the parental chromosomes were randomly involved in the translocation . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
A decrease in BCR / ABL fusion product was observed ( by FISH analysis ) after incubation of BM cells from CML patients in liquid culture for 7 days with 10 ( 9 ) M ARA C or 10 ( 7 ) M Eilatin in the presence of IL 11 alone or in combination with other cytokines . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The hypothesis that minor bcr / abl fusion mRNA is produced in blast crisis of chronic myelogenous leukemia ( CML ) is examined . ^^^ The RNA transcripts encoding the minor and major bcr / abl fused protein were detected by polymerase chain reaction ( PCR ) using RNA from peripheral blood or bone marrow cells of eight patients with blast crisis or accelerated phase of CML . ^^^ In two of these four patients , samples of initial diagnosis of chronic phase of CML were available , which did not show minor bcr / abl transcript . ^^^ We conclude that the appearance of minor bcr / abl mRNA transcript is associated with the terminal evolution of CML in lymphoblastic crisis . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
It is suggested that each laboratory define its own threshold of bcr / abl fusion signals for diagnosing Ph positive CML by FISH . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We called this type of translocation `` segmental jumping translocation ( SJT ) . ' ' SJT of the ABL oncogene was not detected in samples from 15 patients with de novo acute myelocytic leukemia ( AML ) , 12 with myelodysplastic syndrome ( MDS ) , or 20 with chronic myelocytic leukemia ( CML ) at the chronic phase . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Characteristic of chronic myelogenous leukemia ( CML ) is the presence of the chimeric p 210 ( bcr abl ) protein possessing elevated protein tyrosine kinase activity relative to normal c abl tyrosine kinase . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
A search for the bcr / abl gene rearrangement should be included with the marrow karyotype to exclude CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The Philadelphia chromosome translocation generates a chimeric oncogene , BCR / ABL , which causes chronic myelogenous leukemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Among 84 consecutive patients with chronic phase Ph positive chronic myeloid leukemia ( CML ) who were investigated for the hybrid BCR / ABL mRNA , in six cases ( 7 % ) the disease mimicked essential thrombocythemia ( ET ) at presentation , because of marked thrombocytosis ( platelet counts ranging from 1003 10 10 ( 9 ) / l to 2800 10 10 ( 9 ) / l ) and moderate leukocytosis ( WBC counts from 10 10 10 ( 9 ) / l to 19 10 10 ( 9 ) / l ) . ^^^ The above results , in conjunction with similar data from a few previously published cases , suggest an association between the above form of CML and b3a2 type of BCR / ABL transcript . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Amplification within bands 9q34 and 22q11 . 2 was consistent with previous descriptions of increased copy number of the CML specific 5 ' BCR 3 ' ABL fusion gene in K 562 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic myelogenous leukemia ( CML ) is a hemopoietic stem cell disorder in which an activated ABL oncogene is expressed and has been shown to play an important role in disease pathogenesis . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Integrin mediated regulation of hematopoiesis : do BCR / ABL induced defects in integrin function underlie the abnormal circulation and proliferation of CML progenitors . ^^^ At the molecular level , CML is characterized by the BCR / ABL gene rearrangement which encodes for the oncoprotein , p210bcr abl . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We have previously shown by reverse transcriptase PCR ( rtPCR ) that CML CD34+ HLA DR cells are enriched for BCR / ABL ( ) hematopoietic progenitor cells ( HPC ) while leukemic HPC reside predominately within CML CD34+ HLA DR+ cells . ^^^ Transduction efficiencies of CML CD34+ HLA DR+ cells ranged from 0 . 4 to 9 . 8 % ( mean 3 . 7 + / 1 . 7 % ) and 6 . 0 to 26 % ( mean 17 . 3 + / 4 . 5 % ) ( n = 5 ) over BSA and FN , respectively . rtPCR analysis for BCR / ABL mRNA of individual G 418 resistant HPC generated from CD34+ HLA DR cells revealed that normal BCR / ABL ( ) HPC were successfully transduced under these experimental conditions . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The BCR / ABL oncogene causes human chronic myelogenous leukemia ( CML ) , a myeloproliferative disease characterized by massive expansion of hematopoietic progenitor cells and cells of the granulocyte lineage . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Preferential sequestration in vitro of BCR / ABL negative hematopoietic progenitor cells among cytokine nonresponsive CML marrow CD34+ cells . ^^^ It is believed that long term cultures of CML marrow cells favor the outgrowth of BCR / ABL negative hematopoietic progenitor cells ( HPC ) and that this phenomenon may be enhanced with negative hematopoietic regulators which can maintain primitive HPC in a quiescent state . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We sought to establish the relationship between BCR ABL transcript numbers measured by competitive two step reverse transcription polymerase chain reaction ( RT PCR ) and cytogenetic status in CML patients treated with IFN alpha . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Thus , it is suggested that FISH is a more sensitive method to detect the bcr / abl fusion gene than conventional cytogenetic analysis for the detection of minimal residual disease in CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Finally , we found that BCR / ABL mRNA negative CFCs and LTC ICs present in DR cells selected from steady state CML marrow could be expanded in large scale SCM+IL 3 cultures . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
A human LIM HOX gene , namely hLH 2 , was highly expressed in chronic myelogenous leukemia ( CML ) and located on chromosome 9q33 34 . 1 , in the same region as the reciprocal translocation that creates the Bcr Abl chimera of Philadelphia chromosome ( H . ^^^ These results suggest that the transcriptional activation of hLH 2 in CML is likely due to a cis acting effect , but not a trans acting effect , of the Bcr Abl fusion protein . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BCR / ABL is a human chimeric oncogene that causes chronic myelogenous leukemia ( CML ) . ^^^ In this review , we will describe the molecular and biological abnormalities in CML and several signal transduction mechanisms utilized by BCR / ABL as compared to hematopoietic growth factors . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
A human LIM HOX gene , namely hLH 2 , was highly expressed in chronic myelogenous leukemia ( CML ) and located on chromosome 9q33 34 . 1 , in the same region as the reciprocal translocation that creates the Bcr Abl chimera of Philadelphia chromosome [ Wu et al . ( 1996 ) Oncogene 12 , 1205 ] . ^^^ These results suggest that the transcriptional activation of hLH 2 in CML is likely due to a cis acting effect , but not a trans acting effect of the Bcr Abl fusion protein . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Pathophysiology of CML : do defects in integrin function contribute to the premature circulation and massive expansion of the BCR / ABL positive clone . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The Philadelphia chromosome , detected in virtually all cases of chronic myelogenous leukemia ( CML ) , is formed by a reciprocal translocation between chromosomes 9 and 22 that fuses BCR encoded sequences upstream of exon 2 of c ABL . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Fluorescence in situ hybridization ( FISH ) is a new technique that allows demonstrating of the bcr / abl gene fusion in bone marrow cells of patients with Philadelphia translocation ( Ph ) positive chronic myeloid leukemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Whether this rare clinical form of CML is associated with single , specific variants of BCR / ABL transcripts is a matter of debate . ^^^ The results of our study together with a review of literature data suggest that different BCR / ABL transcript variants may occur in CML mimicking ET , without an apparently significant prevalence of one type . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
CML , characterized by the BCR / ABL gene rearrangement has been more extensively studied than any other malignancy . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Cosmid probes specific for the major BCR / ABL rearrangement ( commercially available probes ) were employed by us to evaluate 134 patients with the clinical diagnosis of chronic myelocytic leukemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
This is the first veprted of case Ph negative , M BCR / ABL positive CML with t ( 9 ; 16 ) accompanied by severe DIC . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Fluorescence in situ hybridization ( FISH ) reveals that in chronic myelogenous leukaemia ( CML ) following interferon alpha therapy , normalization of megakaryocyte size is associated with the loss of bcr / abl translocation . ^^^ CONCLUSIONS : A normalization of megakaryocyte size following IFN therapy in CML is significantly associated with a loss of the bcr / abl translocation site and therefore indicates a ( partial ) recovery of normal haematopoiesis . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
A BCR / ABL negative chronic myeloid leukemia ( CML ) with t ( 12 ; 14 ) ( p 12 ; q 11 13 ) as the sole chromosomal abnormality was investigated by fluorescence in situ hybridization ( FISH ) , which disclosed a cryptic insertion of ETV 6 ( previously called TEL ) , located at 12p12 , into ABL at chromosome band 9q34 . ^^^ ETV6 / ABL chimeric transcripts have previously been reported in acute leukemias , but never before in CML . ^^^ The present case suggests that ETV6 / ABL positivity may constitute a new genetic subgroup of BCR negative CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Aristeromycin isolated as an Abl function inhibitor induced erythroid differentiation in human CML K 562 cells . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic myelogenous leukemia ( CML ) is a malignant disease of the human hematopoietic stem cell caused by the BCR / ABL gene rearrangement . ^^^ The presence of the BCR / ABL oncoprotein is necessary and sufficient for malignant transformation seen in CML . ^^^ We thus hypothesized that transfer of a vector that combines a drug resistance gene with anti BCR / ABL antisense ( AS ) sequences may allow for posttransplant chemotherapy to decrease persistent disease while rendering inadvertently transduced CML stem and progenitor cells functionally normal . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We previously reported that the abl promoter ( Pa ) undergoes de novo DNA methylation in the course of chronic myelocytic leukemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Second , the number of committed ( CD34+ / CD38+ ) and non committed ( CD34+ / CD38 ) stem cells , expressing the chimeric fusion gene p 210 BCR / ABL in the autograft from a patient with chronic myeloid leukemia ( CML ) , was determined . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Pseudo Gaucher histiocytes identified up to 1 year after transplantation for CML are BCR / ABL positive . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
A new case of chronic myeloid leukemia ( CML ) in myeloid blast crisis with an atypical ( b3 / a3 ) junction of the BCR / ABL gene . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Of the three categories of innovative therapies , two are based on studies that demonstrate the bcr / abl gene rearrangement in the pathogenesis of CML , whereas the third is based on the observation that allogeneic disparity is important to maintain remissions in CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The 9 ; 22 chromosomal translocation characteristic of CML results in a fused bcr / abl gene and an abnormal fusion protein , p210bcr / abl . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In 12 CML patients surviving more than 3 months , PCR analysis of the BCR / ABL transcript showed that minimal residual disease after T cell add back was transient except in two patients who developed hematological relapse . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
CML is associated with increased abl oncogene protein tyrosine kinase ( PTK ) activity . ^^^ These data suggest that the relative resistance of CML progenitor cells to therapeutic drugs and the lack of response to MIP 1alpha occurs as a direct consequence of abl PTK activity and involves desensitisation of signal transduction events stimulated by MIP 1alpha receptors . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The BCR / ABL gene product of the Philadelphia ( Ph ) chromosome induces chronic myelogenous leukemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
It appears that Fas mediated downmodulation of p 210 bcr / abl restores susceptibility to apoptosis of CML cells ; in addition , in vitro studies on CML cells may predict response to IFN alpha treatment . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Quantitative reverse transcription polymerase chain reaction ( Q RT PCR ) assessing the amount of transcripts of the BCR / ABL gene , the molecular marker of chronic myeloid leukemia ( CML ) , is the only method sensitive enough for monitoring of minimal residual disease ( MRD ) in CML patients after bone marrow transplantation ( BMT ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Following the discovery of the p210bcrabl protein product of the bcrabl chimeric fusion gene generated by the Philadelphia chromosome translocation in chronic myelogenous leukemia ( CML ) , structure function studies quickly identified which parts of this molecule were playing a role in the generation of the phenotypes of growth factor independent growth , anchorage independent growth , and genetic instability which are associated with this disease . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Detection of bcr / abl mRNA in a case of chronic myelogenous leukemia in long term remission : CML or sensitivity of detection . ^^^ We report a case of CML with clinical and hematologic remission for 19 years after two cycles of busulphan not causing medullar aplasia , negative for the BCR / ABL gene by Southern blot but with the gene ' s mRNA detectable by hot start nested RT PCR . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We used two color fluorescence in situ hybridization ( FISH ) to detect BCR / ABL fusion in interphase nuclei in bone marrow of 17 patients with chronic myeloid leukemia ( CML ) before and in the course of interferon therapy . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Expression of the 210 kD bcr / abl fusion oncoprotein can cause a chronic myelogenous leukemia ( CML ) like disease in mice receiving bone marrow cells transduced by bcr / abl encoding retroviruses . ^^^ To overcome this limitation , we have developed an efficient and reproducible method for inducing a CML like disease in mice receiving P 210 bcr / abl transduced bone marrow cells . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Previous studies suggest that abnormal integrin function in CML progenitors is related to the presence of the BCR / ABL oncogene . ^^^ BCR / ABL may alter integrin function in CML by phosphorylating cytoskeletal and / or signaling proteins important for normal integrin function . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We investigated the influence of cell composition on the percentage of positive FISH signals in 17 BCR / ABL positive leukapheresis products from 12 CML patients . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We report an RNA targeting strategy , which selectively degrades bcr / abl mRNA in chronic myelogenous leukemia ( CML ) cells . ^^^ Selective degradation of the targeted RNA sequences was demonstrated in assays with purified RNase L and decreases of p 210 ( bcr / abl ) kinase activity levels were obtained in the CML cell line , K 562 . ^^^ The control oligonucleotides had either reduced or no effect on CML cell growth and bcr / abl mRNA levels . ^^^ These findings show that CML cell growth can be selectively suppressed by targeting bcr / abl mRNA with 2 5A antisense for decay by RNase L and suggest that these compounds should be further explored for their potential as ex vivo purging agents of autologous hematopoietic stem cell transplants from CML patients . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic myelogenous leukemia ( CML ) is characterized by the Philadelphia ( Ph ) translocation and BCR / ABL gene rearrangement which occur in a pluripotent hematopoietic progenitor cell . ^^^ To show the clonal nature of Ph CD 34 ( + ) HLA DR CML progenitors , we have compared the expression of BCR / ABL mRNA with 10 chromosome inactivation patterns ( HUMARA ) in mononuclear cells and in CD 34 ( + ) HLA DR+ and CD 34 ( + ) HLA DR progenitors in marrow and blood obtained from 11 female CML patients ( 8 in chronic phase and 3 in accelerated phase [ AP ] disease ) . ^^^ In contrast to ECP CML , steady state marrow progenitors in late chronic phase and AP disease were mostly Ph+ , BCR / ABL mRNA+ , and clonal . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We describe a pediatric case of acute promyelocytic leukemia with an 1 ( 17q ) after treatment of BCR / ABL positive chronic myeloid leukemia ( CML ) for 3 . 5 years . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In conclusion , monitoring of CML patients by quantification of the bcr abl protein is a feasible and sensitive alternative to chromosomal analysis of bone marrow . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Because of the probable causal relationship between constitutive p 210 ( bcr / abl ) protein tyrosine kinase activity and manifestations of chronic phase chronic myelogenous leukemia ( CML ; myeloid expansion ) , a key goal is to identify relevant p 210 substrates in primary chronic phase CML hematopoietic progenitor cells . ^^^ Because recent evidence has clearly implicated both PI ( 3 , 4 , 5 ) P 3 and PI ( 3 , 4 ) P 2 in growth factor mediated signaling , our finding that both SHIP 1 and SHIP 2 are constitutively tyrosine phosphorylated in CML primary hematopoietic progenitor cells may thus have important implications in p 210 ( bcr / abl ) mediated myeloid expansion . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Detection of the bcr / abl gene in bone marrow macrophages in CML and alterations during interferon therapy a fluorescence in situ hybridization study on trephine biopsies . ^^^ A fluorescence in situ hybridization ( FISH ) study was performed on trephine biopsies of the bone marrow in chronic myelogenous leukaemia ( CML ) to evaluate the bcr / abl translocation in macrophages before and during interferon ( IFN ) therapy . ^^^ Moreover , clinical remission and reduction of bcr / abl positive macrophages under IFN therapy lend support to the hypothesis that the presence of malignant stromal macrophages may contribute to the selective expansion of leukaemic precursors and the suppression of normal haematopoiesis in CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Philadelphia ( Ph ) chromosome or the bcr / abl fusion gene is the hallmark of chronic myeloid leukemia ( CML ) and serves as a prognostic marker during its treatment . ^^^ The present study indicates that FISH analysis in the peripheral blood is a simple and reliably sensitive test for the detection and quantitative monitoring of the M bcr / abl fusion gene in CML in routine clinical practice , although this can not entirely replace karyotype analysis of bone marrow cells . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Blood samples from a patient who recently received an inadvertent transfusion of CML cells were evaluated for the presence of the bcr / abl translocation characteristic of CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Here , we show that the expression of bcr / abl in CIK cells generated from patients with CML correlates with progression of disease in individual patients . ^^^ In addition , progression of disease from chronic phase to accelerated phase could be predicted in two patients by studying the expression of bcr / abl in CIK cells generated from CML patients . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Abnormal ABL related protein with increased tyrosine kinase activity suggested a molecular mechanism of CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In addition , 33 / 75 ( 44 per cent ) of mice sacrificed between 7 and 35 weeks following injection of CML cells were bcr / abl positive in the bone marrow and 17 / 70 ( 24 per cent ) were positive in the spleen . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Detection of BCR ABL transcripts in chronic myeloid leukemia ( CML ) using a ' real time ' quantitative RT PCR assay . ^^^ Quantitative competitive RT PCR techniques have been developed to detect BCR ABL fusion transcripts in CML but they are hardly reproducible . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Fluorescence in situ hybridization ( FISH ) showed that only some CD1a+ / CD14 DC derived from BM of patients with CML expressed the bcr / abl fusion gene . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Philadelphia ( Ph ) or BCR / ABL negative cells with immature phenotype ( CD 34 positive , DR negative ) can be recovered from patients with chronic myeloid leukemia ( CML ) in chronic phase . ^^^ By contrast , LTC cells or secondary colonies obtained from CML CD34+ cells without culture in the presence of 5 FU were always positive for BCR / ABL rearrangement . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Fluorescent in situ hybridization of CI activated CML cells confirmed their leukemic origin by displaying the typical bcr / abl fusion signal . ^^^ No difference in bcr / abl translocation percentages between untreated and CI treated CML nuclei was observed . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
CML with exclusive expression of ALL type bcr / abl has only been rarely described . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Abnormal circulation and unregulated proliferation of chronic myelogenous leukemia ( CML ) progenitors is related , at least in part , to BCR / ABL induced abnormalities in beta 1 integrin mediated adhesion and signaling . ^^^ In the present study , we evaluated whether abnormalities in beta 1 integrin cytoskeletal interactions were present in primary CML progenitors and contributed to defective integrin function . beta 1 integrin cytoskeletal interactions were studied in CML and normal CD34+ primary hematopoietic progenitors as well as BCR / ABL transfected or mock transfected M07e cells . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Concomitant expression of the rare E1 / A3 and B2 / A3 types of BCR / ABL transcript in a chronic myeloid leukemia ( CML ) patient . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The BCR / ABL hybrid gene plays a central role in the pathogenesis of the chronic phase of chronic myeloid leukemia ( CML ) . ^^^ We used a very sensitive quantitative reverse transcriptase polymerase chain reaction to investigate the levels of hybrid BCR / ABL mRNA in bone marrow cells of 20 patients with Philadelphia positive ( Ph ( + ) ) CML treated with interferon alpha ( IFN alpha ) as a single agent . ^^^ These results indicate that downmodulation of BCR / ABL gene expression could be one of the mechanisms involved in the response of CML patients to IFN alpha treatment . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
RESULTS : Incubation of CML PBPC over 48 h in suspension culture with 100 microM CGP57148B reduced the proportion of bcr / abl positive colonies to 4 . 4 + / 4 . 3 % ( n = 5 ) after direct plating , 6 . 6 + / 4 . 2 % ( n = 5 ) after 2 weeks LTC and 5 + / 5 . 6 % ( n = 2 ) after 6 weeks LTC . ^^^ Following long term exposure to CGP57148B at a concentration of 1 microM , the proportion of remaining bcr / abl positive colonies was 35 % , 9 % and 25 % of untreated CML samples after direct plating as well as after 2 and 6 weeks LTC , respectively . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We report here a case of AA treated successfully with antilymphocytic globulin and cyclosporin in whom Ph 1 negative , BCR / ABL negative CML developed 8 years after diagnosis of AA . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The BCR / ABL oncogene causes chronic myelogenous leukemia ( CML ) , a myeloproliferative disorder characterized by clonal expansion of hematopoietic progenitor cells and granulocyte lineage cells . ^^^ In a series of BCR / ABL transformed hematopoietic cell lines , Philadelphia chromosome ( Ph ) positive cell lines , and primary cells from patients with CML , the expression of SHIP was found to be absent or substantially reduced compared to untransformed cell lines or leukemia cells lacking BCR / ABL . ^^^ The reduction of SHIP due to BCR / ABL is likely to directly contribute to the pathogenesis of CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We have also transfected freshly isolated CD34+ bone marrow cells from patients with CML with the DNAzymes , which specifically inhibited the growth of bcr abl positive CFU Mix colonies by 53 80 % . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In most patients with chronic myelogenous leukemia ( CML ) primitive hematopoietic progenitors carry the acquired reciprocal bcr / abl gene rearrangement t ( 9 ; 22 ) ( q34 . 1 ; q11 . 21 ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Methylation of the proximal promoter of the ABL 1 oncogene is a common epigenetic alteration associated with clinical progression of chronic myeloid leukemia ( CML ) . ^^^ In cell lines established from CML blast crisis , which only carry a single ABL 1 allele nested within the BCR ABL fusion gene , ABL 1 promoters were universally methylated . ^^^ Furthermore , ABL 1 methylation was noted in the vast majority of colonies from blast crisis , but not chronic phase CML . ^^^ Our data suggest that specific methylation of the Ph ' associated ABL 1 allele accompanies clonal evolution in CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Short term culturing influences the number of bcr / abl fused cells detected by fluorescence in situ hybridisation in bone marrow aspirates of CML patients . ^^^ Fluorescence in situ hybridisation ( FISH ) has been proven as a helpful tool in diagnosis and monitoring of bcr / abl fusion in chronic myelogeneous leukaemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
OBJECTIVE : To study the bcr / abl fusion gene in chronic myeloid leukemia ( CML ) cases with Philadelphia chromosome ( Ph ) negative , and variant Ph translocations and other chromosome anomalies . ^^^ The existence of negative bcr / abl fusion gene CML implies that some other initial events inducing CML might have occurred in such cases . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In conclusion , the establishment of an in vitro and in vivo CML model using UT 7 cells suggests for the first time in human cells , that the fully transformed phenotype induced by BCR ABL requires high levels of BCR ABL expression . ^^^ These findings suggest that variable levels of BCR ABL in primary patient cells could also be responsible for the different phenotypic features seen in chronic and acute phases of CML , such as the differentiation ability induced by growth factors . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Acquired loss of p 53 induces blastic transformation in p 210 ( bcr / abl ) expressing hematopoietic cells : a transgenic study for blast crisis of human CML . ^^^ To investigate whether loss of p 53 plays a role in the evolution of CML , we crossmated p 210 ( bcr / abl ) transgenic ( BCR / ABL ( tg / ) ) mice with p 53 heterozygous ( p 53 ( + / ) ) mice and generated p 210 ( bcr / abl ) transgenic , p 53 heterozygous ( BCR / ABL ( tg / ) p 53 ( + / ) ) mice , in which a somatic alteration in the residual normal p 53 allele directly abrogates p 53 function . ^^^ Our study presents in vivo evidence that acquired loss of p 53 contributes to the blastic transformation of p 210 ( bcr / abl ) expressing hematopoietic cells and provides insights into the molecular mechanism for blast crisis of human CML . ( Blood . 2000 ; 95 : 1144 1150 ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The BCR / ABL fusion protein is a constitutively active tyrosine kinase that is responsible for the pathogenesis of chronic myelogenous leukemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In the prospective study , we examined hematopoietic mixed chimerism ( using polymerase chain reaction ( PCR ) of variable number of tandem repeat VNTR sequences ) and minimal residual disease ( MRD ) status ( using qualitative and in the case of positivity quantitative reverse transcriptase polymerase chain reaction ( RT PCR ) for the BCR / ABL fusion mRNA ) in serial peripheral blood samples taken from 25 patients after bone marrow transplantation ( BMT ) for chronic myeloid leukemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The bcr / abl fusion mRNA is present in all CML patients , whereas the reciprocal abl / bcr fusion mRNA is detectable in about 80 % of the Ph+ CML patients . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Two of 19 CML patients in the blastic phase ( 10 . 5 % ) had an extra fused BCR ABL gene on structurally complex chromosome aberrations in addition to the Ph chromosome . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
OBJECTIVE : To determine whether the compound STI 571 ( formerly known as CGP571418B ) , a selective inhibitor of the protein tyrosine kinase ( PTK ) activity of ABL and BCR ABL proteins , preferentially reduces the capacity for amplification of granulocyte macrophage progenitors ( CFU GM ) from patients with chronic myeloid leukemia while sparing normal CFU GM and to compare responses of CML and normal cells with STI 571 and IFN alpha . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In this study , we investigated the immunogenicity in patients with chronic myeloid leukemia ( CML ) of a 17 mer b3 / a2 Bcr / abl peptide ( B / A1 ) , which was shown to induce proliferative responses in lymphocytes from normal donors . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The BCR ABL chimeric protein is thought to play a central role in the pathogenesis of Philadelphia ( Ph ) chromosome positive leukemias , notably chronic myeloid leukemia ( CML ) . ^^^ In this study , we used differential display to investigate the alterations of gene expression in BV 173 , a CML cell line derived from lymphoid blast crisis , after exposure to ST 1571 , which selectively inhibits ABL PTK activity . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We used a sensitive , quantitative bisulfite PCR assay , methylation sensitive single nucleotide primer extension ( Ms SNuPE ) , to measure methylation of the 5 ' CpG islands of c abl and p 15 in chronic myelogenous leukemia ( CML ) patients during progression . ^^^ We found that the Pa promoter of c abl was methylated in 81 % ( 17 / 21 ) of the white blood cells ( WBCs ) of CML patients , which correlates with previous reports . ^^^ Methylation of the p 15 but not c abl Pa promoters was associated with CML progression ( P = 0 . 047 vs 0 . 46 ) , and the two events were independently acquired . ^^^ We conclude that de novo methylation of c abl and p 15 both occur in CML , and analysis of DNA methylation changes using the bisulfite based MS SNuPE assay allows both a sensitive and quantitative assessment of these molecular events compared to other methods currently utilized . ( Blood . 2000 ; 95 : 2990 2992 ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chimeric bcr / abl fusion proteins are thought to be the molecular ' pathogen ' of chronic myelogenous leukaemia ( CML ) . ^^^ Our data show that ongoing or relapsing CML is paralleled by increasing peripheral levels of bcr / abl fusion RNAs . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
These observations provide a unique opportunity to identify cellular factor ( s ) which regulate BCR / ABL kinase in vivo and suggests possible novel treatment of CML by a mild hyperthermia . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In chronic myeloid leukemia ( CML ) ex vivo generated DC are characterized by constitutive expression of bcr / abl and possibly other yet undefined leukemia associated antigens , since these DC share a common progeny with leukemic cells . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Thus , presence of BCR / ABL induces elevated levels of p 27 ( Kip ) and relocation of p 27 ( Kip ) to the cytoplasm , which contributes to the loss of integrin mediated proliferation inhibition , characteristic of CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Methylation of the proximal promoter of the ABL 1 oncogene is common epigenetic alteration associated with clinical progression of chronic myeloid leukemia ( CML ) . ^^^ In cell lines established from CML blast crisis , which only carry a single ABL 1 allele nested within the BCR ABL fusion gene , ABL 1 promoters were universally methylated . ^^^ ABL 1 methylation was was noted in the vast majority of colonies from blast crisis , but not chronic phase CML . ^^^ These data suggest that specific methylation of the Ph ' associated ABL 1 allele accompanies clonal evolution in CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The Philadelphia chromosome , t ( 9 ; 22 ) ( q 34 ; q 11 ) gives rise more frequently , in chronic myeloid leukaemia ( CML ) , to two BCR / ABL chimeric transcripts differing only by the absence of 75 nucleotides and defined as b2a2 and b3a2 types , encoding two 210 kDa tyrosine kinase proteins differing only by the absence of 25 amino acids coded by the b 3 exon . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Molecular analysis of bcr / abl mRNA was performed on single CML colonies by nested reverse transcriptase polymerase chain reaction . ^^^ Evaluation of bcr / abl transcript on residual CML colonies incubated with TGF beta 3 demonstrated a small subset of neoplastic CD34+ cells unresponsive to the inhibitory effect of the study cytokine . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Recurrence of polyarthritis and exacerbation of psoriasis were observed in parallel with a significant increase in the proportion of male ( host ) DNA , and 5 % of the mitoses were bcr / abl positive , indicating an increase in the clone of CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Targeting the tyrosine kinase activity of Bcr Abl with STI 571 is an attractive therapeutic strategy in chronic myelogenous leukemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BACKGROUND : Among patients diagnosed with chronic myeloid leukemia ( CML ) , a small percentage lack a BCR / ABL fusion gene , a landmark of CML . ^^^ Their clinical features are distinct from patients with BCR / ABL positive CML , although to the authors ' knowledge the pathogenesis to date has been unknown . ^^^ METHODS : A 50 year old female patient with BCR / ABL negative CML and multiple complications of Graves disease , Sweet syndrome , and a fatal pulmonary alveolar proteinosis ( PAP ) is described in the current study . ^^^ CONCLUSIONS : In the patient in the current study , hyperfunction of the neutrophils might have contributed to the onset of PAP as well as Sweet syndrome and to the pathogenesis of BCR / ABL negative CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
For this purpose , we analyzed by FISH 24 healthy volunteer donors , 31 patients affected by non chronic myelogenous leukemia ( CML ) hematological malignancies , 47 CML patients at diagnosis , and 82 CML patients during treatment for the BCR / ABL fusion . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Exposure to low dose cytosine arabinoside ( Ara C ; 10 nmol / L ) increased hemoglobin levels in HL 60 / Bcr Abl and in the chronic myeloid leukemia ( CML ) blast crisis K 562 cells , which express the p 210 Bcr Abl protein . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The inadvertent activation of the Abelson tyrosine kinase ( Abl ) causes chronic myelogenous leukemia ( CML ) . ^^^ A small molecule inhibitor of Abl ( STI 571 ) is effective in the treatment of CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
METHODS : We studied six patients with chronic myelogenous leukaemia ( CML ) carrying the BCR / ABL fusion gene in their bone marrow derived cells . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic myelogenous leukemia ( CML ) , a malignancy of a hematopoietic stem cell , is caused by the Bcr Abl tyrosine kinase . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We have developed a quantitative real time PCR ( QC PCR ) method in the LightCycler , based on the use of fluorescently labeled probes ( HybProbes ) , to estimate BCR ABL fusion gene transcripts in samples from CML patients . ^^^ Besides , the results of BCR ABL quantification in the follow up of patients clearly confirm that real time PCR with HybProbes is a reliable and sensitive method for monitoring minimal residual leukemia after HSCT in CML patients . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Only DCs obtained from CML patients at diagnosis exhibited bcr / abl fusion gene when tested by fluorescent in situ hybridization ( FISH ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The effect of mutations in the Src homology 2 ( SH 2 ) domain of the BCR / ABL oncogene on leukemogenesis was tested in a quantitative murine bone marrow transduction / transplantation assay that accurately models human Philadelphia positive B lymphoid leukemia and chronic myeloid leukemia ( CML ) . ^^^ Under conditions where the p 190 and p 210 forms of BCR / ABL induce fatal CML like myeloproliferative disease within 4 weeks , p 210 SH2 mutants induced CML like disease in some mice only after a significant delay , with other recipients succumbing to B lymphoid leukemia instead . ^^^ In contrast , p 190 BCR / ABL SH 2 point and deletion mutants rapidly induced CML like disease . ^^^ Hence , the decreased induction of CML like disease by the p 210 BCR / ABL SH 2 mutants is not due to impaired activation of PI 3 kinase . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The CML blood derived colonies were isolated and analyzed by FISH for BCR / ABL sequences . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The deregulated tyrosine kinase activity of the BCR ABL fusion protein is the cause of malignant transformation in almost all cases of chronic myelogenous leukaemia ( CML ) , making BCR ABL an ideal target for pharmacological inhibition . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In this study , we compared Bcr Abl / p210 and 5 Abl / p160 in this mouse CML model . ^^^ The Bcr Abl / p210 fusion protein plays a primary role in the pathogenesis of chronic myelogenous leukemia ( CML ) . ^^^ We have recently shown that expression of Bcr Abl in bone marrow cells by retroviral transduction efficiently induces a myeloproliferative disorder in mice resembling human CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BCR / ABL , the oncoprotein responsible for chronic myeloid leukemia ( CML ) , transforms hematopoietic cells through both Ras dependent and independent mechanisms . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BACKGROUND AND OBJECTIVES : The most common translocation in chronic myeloid leukemia ( CML ) t ( 9 ; 22 ) ( q 34 ; q 22 ) produces the BCR / ABL fusion gene . ^^^ We set up and evaluated a rapid and reliable real time reverse transcription polymerase chain reaction ( RT PCR ) approach using TaqMan technology for detection and quantification of bcr abl transcripts in CML patients at diagnosis and during therapy . ^^^ To determine the utility of the assay , we quantified the bcr abl / ABL Ia ratio in 59 bone marrow samples ( 45 samples with evidence of different Ph+ chromosome percentages and 14 samples in complete cytogenetic remission ) from 48 CML patients , 34 of them at diagnosis and 14 in clinical remission ( CR ) . ^^^ We conclude that this real time RT PCR procedure is a reliable and sensitive method of monitoring CML patients after therapy , and that the bcr abl / ABL Ia ratio correlates strongly with cytogenetic analysis . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
OBJECTIVE : To investigate the effect of bcr / abl fusion gene on the growth of chronic myeloid leukemia ( CML ) cells and to explore the feasibility of ribozyme in CML gene therapy . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
STI 571 ( CGP57148B ) is an inhibitor of BCR / ABL , the cause of chronic myeloid leukaemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
STI 571 : targeting BCR ABL as therapy for CML . ^^^ Results of clinical trials to date have demonstrated the crucial role of the bcr abl tyrosine kinase in chronic myelogenous leukemia ( CML ) pathogenesis and the potential of anticancer agents designed to target specific molecular abnormalities in human cancer . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Here , we demonstrate that when K 562 chronic myelogenous leukemia ( CML ) cells are adhered to fibronectin ( FN ) , they become resistant to apoptosis induced by the BCR / ABL inhibitors AG 957 and STI 571 , as well as DNA damaging agents and gamma irradiation . ^^^ Antagonists of beta 1 integrin mediated adhesion or corresponding signal transduction elements may sensitize CML cells to chemotherapy and prevent resistance to the novel BCR / ABL kinase inhibitors being used for the treatment of this disease . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The ataxia telangiectasia gene , ATM , is a candidate gene for this transformation because the complex karyotypes associated with BC of CML suggest that DNA double strand break repair is defective and because the ABL pathway involves the interaction between the Abl and the Atm proteins . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
As the clinical course and peripheral blood findings were different from blastic crisis of chronic myelogenous leukemia ( CML ) and CML with minor bcr / abl chimeric mRNA , the present case was diagnosed as `` multiphenotypic acute leukemia ' ' , a type of acute basophilic leukemia classified by Duchayne . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
A linear correlation between quantities of WT 1 and bcr / abl fusion transcripts could be seen in CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
A woman with Ph positive chronic myeloid leukaemia ( CML ) with an atypical e1a3 BCR ABL hybrid gene is described . ^^^ To our knowledge , this is the first report of this transcript type as a unique naturally occurring BCR ABL fusion in a CML patient . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Formation of the hybrid BCR ABL gene is responsible for > 95 % of chronic myeloid leukemia ( CML ) . ^^^ The alternative , downstream ABL promoter ( Pa ) , which is usually retained in this chimeric oncogene , was reported to be methylated in many CML patients , but there has been controversy as to whether this methylation is a frequent change in bone marrow ( BM ) in early chronic phase ( CP ) or only past this stage . ^^^ Also , the relevance of Pa promoter methylation to BCR ABL expression in CML is unclear . ^^^ BM from seven CP CML patients at diagnosis had about 20 60 % of the copies of the ABL Pa promoter methylated . ^^^ Surprisingly , 18 49 % of the CML derived colonies with this methylation reproducibly had no detectable BCR ABL RNA on nested reverse transcription PCR . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic Myeloid Leukemia ( CML ) , a myeloproliferative disease of stem cell origin , is characterized by the presence of the Philadelphia ( Ph ) chromosome and the bcr abl oncogene . ^^^ The BCR ABL fusion gene product , thought to be causative in CML , has multiple effects on diverse cell functions such as growth , differentiation and turnover as well as adhesion and apoptosis . ^^^ Nonetheless , with the efficacy of the ABL tyrosine kinase inhibitor STI 571 ( signal transduction inhibitor 571 ) as a novel therapy in CML recently being realized in clinical trials , it is therefore timely to review our current understanding of the cell biology of this fascinating disease . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic myelogenous leukemia ( CML ) represents an ideal target for a therapy using a selective inhibitor of the BCR ABL tyrosine kinase . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
OBJECTIVE : To define the relationship between Ph chromosome and BCR / ABL mRNA expression in chronic myeloid leukemia ( CML ) patients , and compare cytogenetic analysis and PCR method . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The tyrosine kinase inhibitor imatinib ( STI 571 , Glivec ) blocks the activity of the BCR / ABL oncogene and induces hematologic remissions in the majority of patients with chronic myeloid leukemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
These results demonstrate the utility of this murine model of CML in the evaluation of novel therapeutic agents against Bcr / Abl induced leukemias . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We describe the clinical activity of the ABL kinase inhibitor STI 571 in a patient with accelerated phase of chronic myeloid leukemia ( CML ) relapsing after a second allogeneic BMT and with minimal levels of donor chimerism . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We conclude that a storage period of up to 96 h has little influence on the detection of a bcr / abl fusion transcript in CML at diagnosis . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The e19a2 BCR / ABL fusion transcript with additional chromosomal aberrations on a new case of chronic myeloid leukemia ( CML ) of mild type . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Serial assays of qualitative ( multiplex and nested ) and quantitative PCR were carried out for detecting and estimating the level of BCR ABL transcripts in 39 CML patients following bone marrow transplantation . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Now , a new molecule specific drug , a ABL tyrosine kinase inhibitor ( STI 571 ) , are developing , which is offering new hope for expanded treatment options for patients with CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Three patients with CML received a series of four infusions of CML specific bcr / abl peptide pulsed autologous DCs . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The NK cell cloning frequency was significantly decreased from CML CD 34 ( + ) HLA DR ( + ) cells compared with cells from normal donors , yet CD 34 ( + ) HLA DR ( + ) cells gave rise to BCR / ABL ( + ) NK cells in some patients . ^^^ In contrast to chronic phase CML , significant numbers of NK cells from advanced phase CML patients were BCR / ABL ( + ) , whereas T cells were always BCR / ABL ( ) regardless of the disease stage . ^^^ This study provides the first evidence that BCR / ABL is responsible for the altered differentiation of NK cells and that the NK cell lineage can be involved with the malignant clone in advanced stage CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The compound specifically inhibits proliferation of 5 Abl and Bcr Abl expressing cells ( including cells from CML patients ) and shows anti tumor activity as a single agent in animal models at well tolerated doses . ^^^ STI 571 ( Glivec , Gleevec ) , a phenylamino pyrimidine derivative , is a potent inhibitor of the Abl tyrosine kinase , which is present in 95 % of patients with chronic myelogenous leukemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
METHODS : We developed a human model of p210BCR / ABL positive CML by transducing normal human umbilical cord blood CD34+ cells with a retroviral vector containing the b3a2 bcr / abl cDNA . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The current study compared the effects of these agents on the survival of K 562 cells , bcr / abl transduced FDC P 1 cells , and myeloid progenitors from patients with chronic myelogenous leukemia ( CML ) compared with healthy donors . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The chromosomal translocation t ( 9 ; 22 ) ( q 34 ; q 11 ) is absolutely crucial for CML and leads to the chimeric gene and protein BCR ABL . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
RESULTS : A novel erythroleukemia cell line ( HIE 1 ) , with original cell genetic marker ( Ph chromosome , bcr / abl fusion gene rearrangement ) , was established from a CML patient in blast crisis , and has been passaged for over 60 generations . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
OBJECTIVE : To investigate the efficacy of autologous bone marrow transplantation ( ABMT ) for patients with chronic myelogenous leukemia ( CML ) after in vitro purging of the graft with bcr / abl antisense oligodeoxynucleotides ( AS ODN ) . ^^^ METHODS : Five CML patients , 2 in chronic phase ( CP ) , 1 in accelerated phase ( AP ) and 2 in blast crisis ( BC ) , all confirmed the presence of b3a2 bcr / abl mRNA by RT PCR ( reverse transcriptase polymerase chain reaction ) . ^^^ CONCLUSION : ABMT with bcr / abl AS ODN purged graft can result in quite long duration of MCR and prolonged CP in some patients with CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We show here that hnRNP A 1 levels are increased in myeloid progenitor cells expressing the p 210 ( BCR / ABL ) oncoprotein , in mononuclear cells from chronic myelogenous leukemia ( CML ) blast crisis patients , and during disease progression . ^^^ To assess the potential role of hnRNP A 1 nucleocytoplasmic shuttling activity in normal and leukemic myelopoiesis , a mutant defective in nuclear export was ectopically expressed in parental and BCR / ABL transformed myeloid precursor 32Dcl3 cells , in normal murine marrow cells , and in mononuclear cells from a CML patient in accelerated phase . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Detection of BCR ABL transcripts in chronic myeloid leukaemia ( CML ) is used to confirm the diagnosis and to monitor residual disease . ^^^ BCR ABL / ABL ratios ranged from 0 . 15 to 1 . 59 ( median 0 . 65 ) in RNA from diagnostic blood or bone marrow of 18 CML patients and were < or =0 . 0001 in 20 normal controls . ^^^ Sequential samples analysed from six CML patients post allogeneic bone marrow transplantation who relapsed and received donor lymphocyte infusions showed BCR ABL / ABL ratios which reflected patient status or treatment . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic myeloid leukemia ( CML ) is genetically characterized by the presence of the reciprocal translocation t ( 9 ; 22 ) ( q 34 ; q 11 ) , resulting in a BCR / ABL gene fusion on the derivative chromosome 22 called the Philadelphia ( Ph ) chromosome . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
INTRODUCTION : The causative oncogene in CML is the BCR / ABL protein tyrosine kinase . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
CONCLUSION : The results may provide a new PTD bcr / abl fusion peptide for the immunotherapy of CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Clinical phase I / II studies with the Abl kinase inhibitor imatinib mesylate ( Gleevec / Glivec , formerly STI 571 ) for the treatment for chronic myelogenous leukemia ( CML ) demonstrated the safety and the remarkable efficacy of this molecularly targeted agent . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The BCR / ABL oncogene causes chronic myelogenous leukemia ( CML ) in humans and a CML like disease , as well as lymphoid leukemia , in mice . p 210 BCR / ABL is an activated tyrosine kinase that phosphorylates itself and several cellular signaling proteins . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Targeting the tyrosine kinase activity of BCR ABL represents a very promising therapeutic strategy in chronic myeloid leukemia ( CML ) . ^^^ Our data support that in CML patients treated with STI 571 , ABL mutations are not restricted to the accelerated phase of the disease and that , at least in some cases , mutations seem to occur prior to STI 571 therapy , probably as second mutational events during the course of CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The translocation ( 9 ; 22 ) in CML N results in the transcription of an e19 / a2 type BCR / ABL mRNA that codes for a 230 kD BCR / ABL protein ( p 230 ) . ^^^ METHODS : The objectives of this study were to quantify and correlate with clinical outcome the p 230 mRNA and protein in patients with CML N , to describe six new patients and the follow up ( with molecular analysis ) of five previously reported patients with CML N , and to review characteristics of all patients with CML N and p 230 BCR / ABL reported to date in the literature . ^^^ RESULTS : Quantitative polymerase chain reaction assays on specimens from the great majority of patients with CML N revealed minimal numbers of molecules of p 230 BCR / ABL transcripts per total RNA . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
A murine model of CML blast crisis induced by cooperation between BCR / ABL and NUP98 / HOXA9 . ^^^ Constitutive activation of tyrosine kinases , such as the BCR / ABL fusion associated with t ( 9 ; 22 ) ( q 34 ; q 22 ) , is a hallmark of chronic myeloid leukemia ( CML ) syndromes in humans . ^^^ Furthermore , these data indicate that despite acquisition of additional mutations , CML blast crisis cells retain their dependence on BCR / ABL for proliferation and survival . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BACKGROUND : Quantitative real time polymerase chain reaction ( Q Rt PCR ) is a new tool in the detection and quantification of the BCR / abl fusion transcripts in chronic myelogenous leukemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Imatinib mesylate , an Abl kinase inhibitor , produces sustained complete hematologic responses ( CHRs ) in chronic myelogenous leukemia ( CML ) patients , but the sequence and timing of morphologic and cytogenetic changes in CML patients during prolonged imatinib mesylate treatment has not been described . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BACKGROUND AND OBJECTIVES : The new Abl tyrosine kinase inhibitor imatinib ( imatinib mesylate , STI 571 ) is very effective in the treatment of patients with chronic myeloid leukemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
OBJECTIVES : The aim of this study was to assess the suitability of a technique based on counter flow centrifugal elutriation ( CCE ) , which should allow one to enrich chronic myeloid leukemia ( CML ) patients ' unstimulated native leukapheresis product ( nLP ) in CD34+ HLADR cells and BCR ABL negative cells . ^^^ METHODS : Six newly diagnosed CML patients were subjected to leukapheresis , and the products were subfractionated with the use of CCE . nLP and all fractions were studied for the presence of CD34+ cells and a proportion of BCR ABL fluorescence in situ hybridization ( FISH ) + cells . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BCR / ABL found in chronic myelogenous leukemia ( CML ) is a hallmark of the constitutively active forms of cytoplasmic tyrosine kinases . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The Abl tyrosine kinase inhibitor STI 571 is effective therapy for stable phase chronic myeloid leukemia ( CML ) patients , but the majority of CML blast crisis patients that respond to STI 571 relapse because of reactivation of Bcr Abl signaling . ^^^ Here we identify mutations of Tyr 253 in the nucleotide binding ( P ) loop of the Abl kinase domain to Phe or His in patients with advanced CML and acquired STI 571 resistance . ^^^ The Abl P loop is a second target for mutations that confer resistance to STI 571 in advanced CML , and the Y253F mutation may impair the induced fit interaction of STI 571 with the Abl catalytic domain rather than sterically blocking binding of the drug . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Three examples of inhibitors of protein kinases are reviewed , including low molecular weight compounds targeting the cell cycle kinases ; a potent and selective inhibitor of the HER1 / HER2 receptor tyrosine kinase , the pyrollopyrimidine PKI 166 ; and the 2 phenyl aminopyrimidine STI 571 ( Glivec ( R ) , Gleevec ) a targeted drug therapy directed toward Bcr Abl , the key player in chronic leukemia ( CML ) . ^^^ Based upon its clear association with disease , the Bcr Abl tyrosine kinase in CML represents the ideal target to validate the clinical utility of protein kinase inhibitors as therapeutic agents . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic myelogenous leukemias ( CML ) are caused by constitutively activated tyrosine kinases , such as BCR / ABL , that confer a proliferative and survival advantage to hematopoietic progenitors but do not affect differentiation . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Early reduction of BCR ABL mRNA transcript levels predicts cytogenetic response in chronic phase CML patients treated with imatinib after failure of interferon alpha . ^^^ We conclude that : ( 1 ) quantitative determination of residual disease with real time RT PCR is a reliable and sensitive method to monitor CML patients on imatinib therapy ; ( 2 ) BCR ABL / ABL ratios correlate well with cytogenetic response ; ( 3 ) in IFN pretreated patients all complete responders to imatinib have evidence of residual disease with the limited follow up available ; and ( 4 ) cytogenetic response at 6 months of therapy in CP patients is predictable with real time RT PCR at 2 months . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Selective inhibition of the BCR ABL tyrosine kinase by imatinib ( STI 571 , Glivec / Gleevec ) is a promising new therapeutic strategy in patients with chronic myelogenous leukemia ( CML ) . ^^^ Sixty six patients with CML in myeloid blast crisis ( n = 33 ) , lymphoid blast crisis ( n = 2 ) , accelerated phase ( n = 16 ) , chronic phase ( n = 13 ) , and BCR ABL positive acute lymphoblastic leukemia ( n = 2 ) resistant to imatinib were investigated . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
These compounds specifically inhibit the proliferation of 5 abl and bcr abl expressing cells and have recently been approved as treatment for chronic myeloid leukaemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We report here an example of this approach that has been used to characterize a complex Ph negative chronic myeloid leukemia ( CML Ph ) case in which the BCR / ABL fusion gene was found located on chromosome 9 . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The Abl kinase inhibitor STI 571 ( imatinib mesylate ) induces haematological remissions in many patients with chronic myeloid leukaemia ( CML ) but advanced stage CML usually becomes resistant to STI 571 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BACKGROUND : Up to 5 % of patients with chronic myelogenous leukemia ( CML ) do not have the Philadelphia ( Ph ) translocation t ( 9 ; 22 ) ( q 34 ; q 11 ) or a bcr / abl molecular rearrangement . ^^^ Although the diagnostic criteria of this entity are still under debate , there is general agreement that patients with Ph negative , bcr / abl negative CML have a severe clinical course that is not affected significantly by current treatment options . ^^^ METHODS : A population of 76 patients with bcr / abl negative CML who had received minimal or no previous therapy was characterized carefully with the intent of investigating clinical and hematologic variables and their association with survival by univariate , correlation , and multivariate analyses . ^^^ A group of 73 patients with Ph negative CML who were not tested for the bcr / abl rearrangement ( bcr / abl unknown ) was analyzed separately and used for extension of the analysis . ^^^ CONCLUSIONS : Bcr / abl negative CML is a distinct clinical entity associated with very poor prognosis . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We have previously shown that the Jak 2 tyrosine kinase is activated in Bcr Abl positive cell lines and blood cells from CML blast crisis patients by tyrosine phosphorylation . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We show here that the CML associated oncogene BCR / ABL induces VEGF gene expression in growth factor dependent Ba / F3 cells . ^^^ BCR / ABL induced VEGF expression may contribute to the pathogenesis and increased angiogenesis in CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In contrast , imatinib potently induces remissions from CML by specific inhibition of the ABL tyrosine kinase . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
More recently , the clinical success of imatinib mesylate ( STI 571 ) , potent competitive inhibitor of the Bcr / Abl protein tyrosine kinase , in the treatment of CML has focused enthusiasm toward molecular targeted therapy for the hematological malignancies . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Efficiency of interphase fluorescence in situ hybridization for BCR / ABL on peripheral blood smears for monitoring of CML patients : a comparison with bone marrow findings . ^^^ Herein , BCR / ABL fusion gene was assessed on 21 PB smears from 16 CML patients in chronic phase . ^^^ The incidence of BCR / ABL ( + ) fusion signals in CD 3 ( + ) T cells of CML patients was 5 . 3 % ( SD + / 1 . 9 ) and did not exceed the normal cut off value of 8 % . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Inhibition of Bcr Abl kinase activity by PD 180970 blocks constitutive activation of Stat 5 and growth of CML cells . ^^^ Chronic myelogenous leukemia ( CML ) is a myeloproliferative disease characterized by the BCR ABL genetic translocation and constitutive activation of the Abl tyrosine kinase . ^^^ Among members of the Signal Transducers and Activators of Transcription ( STAT ) family of transcription factors , Stat 5 is activated by the Bcr Abl kinase and is implicated in the pathogenesis of CML . ^^^ In this study , we show that blocking Bcr Abl kinase activity using PD 180970 in the human K 562 CML cell line resulted in inhibition of Stat 5 DNA binding activity with an IC ( 50 ) of 5 nM . ^^^ To detect activated Stat 5 in CML patient specimens , we developed an immunocytochemical assay that can be used as a molecular end point assay to monitor inhibition of Bcr Abl signaling . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Natural killer ( NK ) cells decrease in function during chronic myelogenous leukemia ( CML ) progression from chronic phase to blast crisis , and they can become BCR / ABL ( + ) late in the disease course . ^^^ This is the first study to show that BCR / ABL , well known for its effects on the myeloid lineage , can alter the function of lymphoid cells , which may be associated with the defect in innate immunity associated with CML progression . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
This 4 anilino 3 quinolinecarbonitrile ( SKI 606 ) ablates tyrosine phosphorylation of Bcr Abl in CML cells and of 5 Abl expressed in fibroblasts . ^^^ Constitutive tyrosine kinase activity of Bcr Abl promotes proliferation and survival of chronic myelogenous leukemia ( CML ) cells . ^^^ Inhibition of Bcr Abl tyrosine kinase activity or signaling proteins activated by Bcr Abl in CML cells blocks proliferation and causes apoptotic cell death . ^^^ The selective Abl kinase inhibitor , STI 571 ( marketed as Gleevec ) , is toxic to CML cells in culture , causes regression of CML tumors in nude mice , and is currently used to treat CML patients . ^^^ Here we describe a p . o . active , dual Src / Abl kinase inhibitor with potent antiproliferative activity against CML cells in culture . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The BCR / ABL tyrosine kinase inhibitor imatinib mesylate ( Gleevec , STI 571 ; Novartis , Basel , Switzerland ) has shown remarkable efficacy in the treatment of chronic myelogenous leukemia ( CML ) , with a high proportion of patients achieving complete cytogenetic responses ( CCRs ) . ^^^ Our results indicate that inhibition of BCR / ABL tyrosine kinase activity by imatinib mesylate does not eliminate malignant primitive progenitors in CML patients . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Imatinib mesylate ( STI 571 , Gleevec , Glivec , a selective inhibitor of the BCR ABL tyrosine kinase causative of chronic myeloid leukemia ( CML ) , represents the paradigm of how a better understanding of the pathogenetic mechanisms of a neoplastic disease can lead to the development of a targeted molecular therapy . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The development of chronic myeloid leukemia ( CML ) is dependent on the deregulated tyrosine kinase of the oncoprotein BCR ABL . ^^^ STI 571 ( imatinib mesylate ) , an abl tyrosine kinase inhibitor , has proven remarkably effective for the treatment of CML . ^^^ In the current study we show that the farnesyl transferase inhibitor ( FTI ) SCH 66336 ( lonafarnib ) inhibits the proliferation of STI 571 resistant BCR ABL positive cell lines and hematopoietic colony formation from peripheral blood samples of STI 571 resistant patients with CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The BCR / ABL chimeric protein plays a central role in the pathogenesis of chronic myelogenous leukemia ( CML ) . ^^^ However , few studies addressed BCR / ABL dependent alterations in gene expression that may contribute to the pathobiology of CML . ^^^ Quantitative real time PCR analysis confirmed that 14 of 14 genes tested were also overexpressed in additional populations of p 210 ( BCR / ABL ) transduced CB CD 34 ( + ) cells , as well as in CD 34 ( + ) cells from primary newly diagnosed CML patients versus GFP transduced CB or samples from normal donors . ^^^ Additional characterization of downstream genes activated by BCR / ABL may lead to important new insights in the molecular mechanisms underlying CML and identify potentially novel therapeutic targets for CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The chronic myelogenous leukemia ( CML ) like myeloproliferative disorder observed in the BCR / ABL murine bone marrow transduction and transplantation model shares several features with the human disease , including a high response rate to the tyrosine kinase inhibitor imatinib mesylate ( STI 571 ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Three new cases are reported of cytogenetically Philadelphia negative ( Ph ) chronic myelocytic leukemia ( CML ) , with positive BCR / ABL gene rearrangement according to a reverse transcriptase polymerase chain reaction technique . ^^^ With the use of BCR / ABL extra signal and CEP 9 probes ( Vysis , Downers Grove , IL , USA ) , FISH studies detected the BCR / ABL fusion gene at the end of chromosome 9 in patient 1 , a BCR / ABL fusion gene on both chromosomes 22 in patient 2 ( who was in an accelerated phase of CML ) , and a BCR / ABL fusion signal on chromosome 22 in patient 3 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
PURPOSE : Imatinib ( Glivec ) is a potent inhibitor of bcr / abl , an oncogenic fusion protein that causes chronic myelogenous leukemia ( CML ) . alpha 1 acid glycoprotein ( AGP ) binds to imatinib with high affinity and inhibits imatinib activity in vitro and in vivo in an animal model . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The diagnosis of CNL requires the exclusion of BCR / ABL positive chronic myelogenous leukaemia ( CML ) and of leukaemoid reactions ( LRs ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
To investigate the significance of duel color fluorescence in situ hybridization ( D FISH ) in monitoring the response to interferon alpha ( IFN alpha ) therapy in patients with chronic myeloid leukemia ( CML ) , the D FISH method was employed to detect the proportion of the interphase nuclei cells with bcr / abl fusion gene in the bone marrow of patients with CML before and after IFN alpha therapy , and the results were compared with those of bcr / abl fusion mRNA by RT PCR and Philadephia chromosome ( Ph ) by conventional cytogenetic analysis . ^^^ In conclusion , D FISH method could directly detect the bcr / abl fusion gene of the interphase cells in bone marrow of patients with CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Imatinib ( ST 1571 ) provides only limited selectivity for CML cells and treatment might be complicated by silent BCR ABL genes . ^^^ Very promising results have been obtained in clinical trials on chronic phase chronic myeloid leukemia ( CP CML ) patients treated with imatinib mesylate ( IM ; Gleevecr , STI 571 ) , a BCR ABL tyrosine kinase inhibitor . ^^^ Moreover , about 30 % of myeloid progenitors ( CFU GM ) from CML BM still formed colonies in the presence of IM , most of which had BCR ABL RNA . ^^^ About half of these treated colonies also displayed methylation of the internal ABL Pa promoter , a CML specific epigenetic alteration , which was used in this study as a marker for BCR ABL translocation containing cells . ^^^ However , ~5 8 % of the treated or the untreated CML BM derived colonies had no detectable BCR ABL RNA by two or three rounds of RT PCR despite being positive for the internal standard RNA and displaying hallmarks of CML , either t ( 9 ; 22 ) ( q 34 ; ql 1 ) or ABL Pa methylation . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Inhibition of the constitutively active Bcr abl tyrosine kinase ( TK ) by STI 571 has proven to be a highly effective treatment for chronic myelogenous leukemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
PCR for the BCR / ABL fusion transcript provides a highly sensitive and specific method for detecting minimal residual disease in patients with chronic myeloid leukemia ( CML ) . ^^^ We sought to determine if quantitative PCR measurement of peripheral blood BCR / ABL transcript can be used to monitor response in CML patients with clinically evident disease while receiving the protein tyrosine kinase inhibitor STI 571 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Expression of MDM 2 , the negative regulator of p 53 , was upregulated in a tyrosine kinase dependent manner in growth factor independent BCR / ABL expressing cells , and in accelerated phase and blast crisis CML samples . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
This review article describes the identification of the tyrosine kinase BCR / ABL as the hallmark of chronic myeloid leukemias ( CML ) as well as the development of a specific inhibitor of this tyrosine kinase , the STI 571 ( Glivec , imatinib mesylate ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The resulting fusion gene , BCR / ABL , encodes an activated tyrosine kinase that can act alone to induce a CML like syndrome in mouse models . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Imatinib ( Gleevec ) ( formerly STI 571 ) competitively targets the adenosine 5 triphosphate ( ATP ) binding site of the kinase domain of ABL and was recently approved for the treatment of chronic myeloid leukemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Imatinib ( Gleevec ) ( formerly STI 571 ) has been shown to selectively inhibit the tyrosine kinase domain of the oncogenic BCR ABL fusion protein of chronic myelogenous leukemia ( CML ) cells . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
To obtain comprehensive information about the genes involved in BCR / ABL dependent leukemogenesis , samples from 15 chronic myelogenous leukemia ( CML ) patients and seven normal donors were analysed using a cDNA microarray assay . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We report the response to the ABL kinase inhibitor imatinib mesylate ( STI 571 ) in a patient with chronic myeloid leukemia ( CML ) who relapsed twice after dose reduced allogeneic stem cell transplantation ( alloSCT ) for B lymphoid blast crisis ( BC ) and failed to develop an antileukemic response despite grade 3 graft versus host disease ( GvHD ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Recently , various mutations within the Abl sequence have been described that negatively affect imatinib binding to Bcr / Abl resulting in cellular resistance of chronic myeloid leukemia ( CML ) cells . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We studied whether the transcription of CD62L in CML cells is dependent on the activity of the BCR ABL tyrosine kinase . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Imatinib mesylate , a competitive inhibitor of Abl tyrosine kinase , is highly effective for the early stages of chronic myelogenous leukemia ( CML ) , but remissions induced in advanced phase CML and Philadelphia chromosome positive ( Ph+ ) acute lymphoblastic leukemia tend to be relatively short lived . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Although the chronic phase of chronic myelocytic leukemia ( CML ) is characterized by the Philadelphia ( Ph ) chromosome creating a hybrid BCR / ABL gene , additional genetic changes involved in blast crisis are poorly understood . ^^^ We report a 4 8 fold amplification by tandem duplication of the BCR / ABL fusion gene clustered on a masked Ph chromosome in a 61 year old male patient with CML in myeloblastic crisis . ^^^ Our finding suggests that the BCR / ABL amplification may play a role as a novel mechanism in the progression to an aggressive blast transformation in some cases of Ph positive CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The inhibition of BCR / ABL tyrosine kinase activity by STI 571 in chronic myeloid leukemia ( CML ) cell lines and CD34+ cells from patients with CML in lymphoid crisis results in induction of BACH 2 expression . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The discovery that some of these genes were located at the breakpoints of chromosome rearrangements in human malignancies , such as the MYC gene in Burkitt ' s lymphoma and the ABL gene in chronic myeloid leukemia ( CML ) has suggested that chromosome abnormalities were causally implicated in the pathogenesis of human diseases . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The BCR / ABL fusion protein is found in more than 90 % of patients with chronic myeloid leukemia ( CML ) as well as in a subset of patients with acute B cell leukemia . ^^^ Although these mice did not display the increase in granulopoiesis commonly found in chronic myeloid leukemia ( CML ) , the phenotype closely resembles a myeloproliferative disorder affecting the megakaryocytic lineage observed in some patients with the BCR / ABL P 210 translocation . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
METHODS : Chronic myelogenous leukemia ( CML ) cell lines or control Bcr / Abl negative cells were treated or not with imatinib mesylate , fixed and permeabilized with formaldehyde followed by methanol ; reacted with rabbit polyclonal and mouse monoclonal antibodies against an epitope including tyrosine 694 of Stat5a ( pSTAT 5 ) ; reacted with antibodies that mark mitotic cells ; counterstained with secondary fluorescent antibodies and 4 ' , 6 diamidino 2 phenylindole ( DAPI ) ; and then subjected to flow cytometry . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
OBJECTIVE : To study the effects of anti ABL tyrosine kinase intrabody on the growth of human chronic myelogenous leukemia ( CML ) cells in nude mice . ^^^ METHODS : A recombinant retroviral vector MSCV ibE IRES eGFP was constructed to express intracellular single chain antibody ( intrabody ) against ABL tyrosine kinase domain in CML cells . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic myeloid leukemia ( CML ) is a clonal neoplastic disorder , characterized by t ( 9 ; 22 ) ( q 34 ; q 11 ) that results in the formation of the Philadelphia chromosome ( Ph ) and the BCR / ABL fusion gene . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Adaphostin ( NSC 680410 ) , an analog of the tyrphostin AG 957 , was previously shown to induce Bcr / abl down regulation followed by loss of clonogenic survival in chronic myelogenous leukemia ( CML ) cell lines and clinical samples . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Philadelphia chromosome negative and bcr / abl negative chronic myeloid leukaemia ( CML ) is an uncommon atypical CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In this paper , we investigated whether ICSBP modulates the growth promoting activity of Bcr / Abl , the causal oncoprotein for CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
It is also notable that the high frequency of BCR ABL mutations and amplifications represents the high degree of heterogeneity in patients with advanced CML , in whom multiple leukemic clones may exist . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Imatinib mesylate is an inhibitor of Bcr / Abl tyrosine kinase , which essentially participates the pathogenesis of chronic myelogenous leukemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
WRN is tyrosine phosphorylated either transiently by treatment of HeLa cells with bleomycin or constitutively in cells from chronic myeloid leukemia ( CML ) patients , and these phosphorylations are prevented by treatment with the Abl kinase inhibitor STI 571 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The use of new nuclei probes in fluorescent in situ hybridization ( FISH ) at diagnosis and during follow up has recently allowed the detection of a deletion of the 5 ' abl region on the derivative chromosome 9 among some CML patients . ^^^ The aim of our study was not only to estimate the frequency of the deletion of the 5 ' abl region among chronic myeloid leukemia ( CML ) patients with bcr abl fusion gene , but also , to assess whether this deletion is concomitant with the formation of the Philadelphia ( Ph ) chromosome or represents a sign for progression of the disease , and finally to evaluate the prognostic implications of this abnormality . ^^^ The deletion of the 5 ' abl region on der ( 9 ) , present in approximately 9 % of the CML , takes place at the same time as the formation of the Ph chromosome translocation and seems of worse prognosis . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
To study effects of a hammerhead ribozyme on chronic myelogenous leukemia ( CML ) cells and bone marrow purging in vitro , a bcr abl specific ribozyme gene was introduced into CML and normal bone marrow cells using retroviral transduction . ^^^ The results suggest that anti bcr abl ribozyme might be used for bone marrow puring of CML cells . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
STI 571 , an abl tyrosine kinase inhibitor , is less effective in chronic myelogenous leukemia ( CML ) patients in the accelerated phase and in blastic crisis . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
CML cells display the translocation t ( 9 ; 22 ) that creates the bcr / abl oncogene . ^^^ The respective oncoprotein ( = BCR / ABL ) exhibits constitutive tyrosine kinase activity and promotes growth and survival in CML cells . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
STI 571 has specific activity in inhibiting c kit , PDGF and Abl receptor tyrosine kinases and has proven successful in the treatment of CML and GIST patients . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Identification of signaling pathways downstream of Abl tyrosine kinase may increase our understanding of the pathogenesis of chronic myelogenous leukemia ( CML ) and suggest strategies to improve clinical treatment of the disease . ^^^ These results suggest that Bcr Abl may regulate translation of critical targets in CML cells via mTOR . ^^^ They also provide a rationale for testing the combination of mTOR inhibitors with the Abl kinase inhibitor imatinib in patients with CML . ^^^ The mTOR inhibitor rapamycin enhanced imatinib mediated killing of CML cell lines in vitro , and it overcame imatinib resistance in cells with Bcr Abl gene amplification . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic myelogenous leukemia ( CML ) is a malignant myeloproliferative disease arising from the clonal expansion of a stem cell expressing the bcr / abl oncogene . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Imatinib mesylate ( tested as STI 571 ) , an abl kinase inhibitor , induces sustained , complete hematologic and cytogenetic responses in chronic myelocytic leukemia ( CML ) patients ; however , emergence of clonal chromosomal aberrations in Philadelphia negative ( Ph ) cells during treatment has been reported . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The Abl tyrosine kinase inhibitor imatinb is becoming a standard for the treatment of chronic myelogenous leukemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Clinical trials in chronic myelogenous leukemia ( CML ) , characterized by the constitutively active Bcr Abl tyrosine kinase , and gastrointestinal stromal tumors , characterized by activating mutations of Kit , have shown excellent results . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BACKGROUND AND OBJECTIVES : Imatinib mesylate ( STI 571 ) is a selective inhibitor of the bcr / abl tyrosine kinase with therapeutic potential in the blast crisis ( BC ) of chronic myelogenous leukemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Imatinib mesylate , an orally administered 2 phenylaminopyrimidine derivative that inhibits BCR / ABL tyrosine kinase activity , has shown great promise in the treatment of chronic myelogenous leukemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Imatinib is a tyrosine kinase inhibitor that binds to ABL proteins and induces cytogenetic remissions in patients with chronic myeloid leukemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
These findings indicate that real time RT PCR , when normalized for the total ABL transcripts , can be used to monitor CML patients during therapy , but we suggest that nested , competitive RT PCR be used to determine BCR ABL / ABL transcript ratios at low transcript values or especially when real time analyses are negative . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In CML , specific inhibition of the elevated ABL tyrosine kinase activity with imatinib is associated with high response rates . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Inhibition of BCR ABL tyrosine kinase activity has shown to be essential for the treatment of chronic myelogenous leukemia ( CML ) . ^^^ However , drug resistance has quickly arisen in recent clinical trials for STI 571 ( Gleevec ) , which is the first approved drug of CML by inhibiting ABL tyrosine kinase . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
One patient with a Philadelphia chromosome negative , BCR / ABL positive CML showed a cytogenetic relapse 6 months after SCM . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic myeloid leukemia ( CML ) is characterized by the expression of the P 210 BCR / ABL fusion protein . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We have previously shown that BCR / ABL , a fusion protein generated by the t ( 9 ; 22 ) ( q 34 ; q 11 ) translocation found in the vast majority of chronic myelogenous leukemia ( CML ) , cooperates with AML1 / MDS1 / EVI1 ( AME ) , a fusion transcription factor generated by a t ( 3 ; 21 ) ( q 26 ; q 22 ) translocation identified as a secondary mutation in some cases of CML during the blast phase ( CML BC ) , in the rapid induction of an acute myelogenous leukemia ( AML ) in mice . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
STI 571 inhibits tyrosine kinase activity of ABL and induces apoptosis of CML cells . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
High incidence of BCR ABL kinase domain mutations and absence of mutations of the PDGFR and KIT activation loops in CML patients with secondary resistance to imatinib . ^^^ We analyzed cytogenetics and screened for mutations of the BCR ABL kinase domain as well as the activation loops of KIT and PDGFRA and B in 49 patients with CML or Ph positive acute lymphoblastic leukemia with resistance to imatinib . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Activating effects of protein transduction domain mediated BCR / ABL protein on CML T cells ] . ^^^ OBJECTIVE : To study the activating effect of protein transduction domain ( PTD ) mediated BCR / ABL protein on T cells from CML patients . ^^^ METHODS : The plasmid containing PTD and b3a2 bcr / abl of CML was constructed by genetic engineering and expressed in E . coli . ^^^ The peripheral blood mononuclear cells from CML patients were stimulated in vitro with purified PTD BCR / ABL protein and the expression of the early activation antigen CD ( 69 ) on CD ( 8 ) ( + ) and CD ( 4 ) ( + ) T cells was detected by flow cytometry ( FCM ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Mutations of the ABL kinase domain ( KD ) are common in patients with chronic myelogenous leukemia ( CML ) who develop resistance to imatinib . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Imatinib mesylate ( STI 571 ) is a competitive Bcr Abl tyrosine kinase inhibitor and has yielded encouraging results in treatment of chronic myelogenous leukemia ( CML ) and gastrointestinal stroma tumors ( GISTs ) . ^^^ In vitro studies have revealed that imatinib mesylate can inhibit growth of cell lines and primitive malignant progenitor cells in CML expressing Bcr Abl . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
For example , BCR / ABL causes chronic myelogenous leukemia ( CML ) , whereas FLT 3 mutations contribute to the pathogenesis of acute myelogenous leukemia . ^^^ The ABL inhibitor Imatinib ( Gleevec , STI 571 ) has remarkable efficacy for treating chronic phase CML , and FLT 3 inhibitors ( e . g . , PKC 412 ) show similar promise in preclinical studies . ^^^ Here , we report that the mTOR inhibitor rapamycin synergizes with Imatinib against BCR / ABL transformed myeloid and lymphoid cells and increases survival in a murine CML model . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
OBJECTIVE : To investigate the relationship between cyclin D 2 and P 210 ( BCR / ABL ) tyrosine kinase in chronic myelogenous leukemia ( CML ) . ^^^ CONCLUSION : Cyclin D 2 is a potential down stream signal molecule of the p 210 ( BCR / ABL ) tyrosine kinase in CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Analysis of CML patients resistant to BCR ABL suppression by Imatinib mesylate coupled with the crystallographic structure of ABL complexed to this inhibitor have shown how structural mutations in ABL can circumvent an otherwise potent anticancer drug . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We examined bone morrow cells of 47 chronic myeloid leukemia ( CML ) cases ( 29 of 47 at the time of diagnosis , 31 of 47 after chemotherapy ) with the bcr / abl translocation probes and of 10 acute promyelocytic leukemia ( APL ) cases ( 7 of 10 at the time of diagnosis , 4 of 10 after chemotherapy ) with the PML / RARalpha translocation probes by using dual color flourescence in situ hybridization ( DC FISH ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BACKGROUND : Despite the efficacy of the BCR ABL tyrosine kinase inhibitor Imatinib mesylate for the treatment of chronic myeloid leukemia ( CML ) , resistance has been observed in a proportion of cases , especially those with advanced stages of the disease . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The Abl kinase inhibitor imatinib mesylate is the preferred treatment for Philadelphia chromosome positive ( Ph ( + ) ) chronic myeloid leukemia ( CML ) in chronic phase but is much less effective in CML blast crisis or Ph ( + ) B cell acute lymphoblastic leukemia ( B ALL ) . ^^^ BCR ABL 1 retrovirus transduced marrow from mice lacking all three Src kinases efficiently induced CML but not B ALL in recipients . ^^^ The kinase inhibitor CGP 76030 impaired the proliferation of B lymphoid cells expressing Bcr Abl in vitro and prolonged survival of mice with B ALL but not CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
A direct binding site for the Grb 2 adapter protein is required for the induction of fatal chronic myeloid leukemia ( CML ) like disease in mice by Bcr Abl . ^^^ Previously , we demonstrated that full length Tel Abl induced two distinct myeloproliferative diseases in mice : CML like leukemia similar to that induced by Bcr Abl and a novel syndrome of small bowel myeloid infiltration endotoxemia and hepatic and renal failure . ^^^ Lack of the Grb 2 binding site had no effect on development of small bowel syndrome but significantly attenuated the induction of CML like disease by Tel Abl . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Regression of the Philadelphia chromosome ( bcr / abl ) positive myelo and megakaryopoiesis after Imatinib ( STI 571 ) therapy in chronic myelogenous leukemia ( CML ) ] . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Using mice with homozygous inactivation of genes encoding the 2 adhesion molecules P selectin and intercellular adhesion molecule 1 ( ICAM 1 ) , we show that the mutant mice develop BCR / ABL induced chronic myeloid leukemia ( CML ) like leukemia at a significantly faster rate than do wild type ( WT ) mice . ^^^ These results indicate that adhesion of BCR / ABL expressing myeloid progenitors to marrow stroma through P selectin and ICAM 1 play an inhibitory role in the development of CML like disease , suggesting that improvement of adhesion between BCR / ABL expressing myeloid progenitor cells and bone marrow stroma may be of therapeutic value for human CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Here we describe how we detected the BCR / ABL fusion gene on the short arm of der ( 9 ) combining classical GTG banding and Fluorescence In Situ Hybridization ( FISH ) in a case of chronic myeloid leukemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Inhibition of wild type and mutant Bcr Abl by AP 23464 , a potent ATP based oncogenic protein kinase inhibitor : implications for CML . ^^^ The deregulated , oncogenic tyrosine kinase Bcr Abl causes chronic myeloid leukemia ( CML ) . ^^^ Imatinib mesylate ( Gleevec , STI 571 ) , a Bcr Abl kinase inhibitor , selectively inhibits proliferation and promotes apoptosis of CML cells . ^^^ AP 23464 , a potent adenosine 5 ' triphosphate ( ATP ) based inhibitor of Src and Abl kinases , displays antiproliferative activity against a human CML cell line and Bcr Abl transduced Ba / F3 cells ( IC ( 50 ) = 14 nM ; imatinib mesylate IC ( 50 ) = 350 nM ) . ^^^ The potency of AP 23464 against imatinib mesylate refractory Bcr Abl and its distinct binding mode relative to imatinib mesylate warrant further investigation of AP 23464 for the treatment of CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
This model has been used to establish the causative role of Bcr / Abl in CML , identify those signaling pathways and regions of Bcr / Abl critical for leukemogenesis , and explore the limitations of targeted CML therapy . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic myelogenous leukemia ( CML ) results from transformation of a primitive hematopoietic cell by the BCR / ABL gene . ^^^ We established a human progenitor model of CML by ectopic expression of BCR / ABL in normal CD34+ cells using retrovirus mediated gene transfer . ^^^ CD34+ cells expressing BCR / ABL demonstrated several features characteristic of primary CML progenitors including increased proliferation in committed and primitive progenitor culture , reduced adhesion to fibronectin , and reduced chemotaxis to stroma derived factor 1alpha . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic myeloid leukaemia ( CML ) is a stem cell disease characterized by an increased production and accumulation of clonal BCR / ABL positive cells in haematopoietic tissues . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In order to evaluate relapse predication ability of STR PCR combining with qualitative RT PCR for the bar / abl transcripts to the patient with chronic myeloid leukemia ( CML ) fulfilled allogeneic stem cell transplantation ( allo HSCT ) , 24 patients with CML after allo HSCT were dynamically investigated for MRD , quantitative analysis of donor chimerism was performed by multiplex PCR amplification of STR markers and capillary electrophoresis with fluorescence detection , qualitative detection of bcr / abl transcripts was detected by nested RT PCR . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BACKGROUND : Short , 21 mer , double stranded / small interfering RNAs ( ds / siRNAs ) were designed to target bcr abl mRNA in chronic myelogenous leukemia ( CML ) with a potential also to target c abl mRNA . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BACKGROUND AND OBJECTIVES : Cytotoxic T lymphocytes ( CTL ) have been generated in vitro against chronic myeloid leukemia ( CML ) associated BCR / ABL specific peptides . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic myelogenous leukemia ( CML ) is characterized by the presence of the chimeric p210bcr / abl oncoprotein that shows elevated and constitutive protein tyrosine kinase activity relative to the normal c abl tyrosine kinase . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The BCR / ABL fusion gene was detected on a paraffin embedded tissue section of the lymph node by double color fluorescence in situ hybridization , indicating an extramedullary hematopoietic tumor of CML origin . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Second hematologic response and disappearance of the ABL gene mutant clone by cessation of imatinib in a CML patient with resistance to imatinib ] . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Biclonal blast crisis with a mutated ABL catalytic domain in a Ph , del ( 9q ) positive CML patient responsive to imatinib : drug resistance should be monitored in all patients irrespective of response status . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Although we still lack a complete definition of all the transformation pathways activated by Bcr Abl , the recent introduction into clinical practice of tyrosine kinase inhibitor represents a major breakthrough to the management of CML and , furthermore , promises to usher in molecularly targeted therapy for other types of leukemia , lymphoma and cancer . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Interestingly , the BCR / ABL fusion gene , which is present in chronic myelogenous leukemia ( CML ) , was also detected in the endothelial cells of patients with CML , suggesting that CML might originate from hemangioblastic progenitor cells that can give rise to both blood cells and endothelial cells . ^^^ Here we isolated fetal liver kinase 1 positive ( Flk1+ ) cells carrying the BCR / ABL fusion gene from the bone marrow of 17 Philadelphia chromosome positive ( Ph+ ) patients with CML and found that these cells could differentiate into malignant blood cells and phenotypically defined endothelial cells at the single cell level . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The BCR / ABL fusion tyrosine kinase activates various intracellular signaling pathways , thus causing chronic myeloid leukemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
This study was to evaluate efficacy of imatinib mesylate , a specific inhibitor of BCR / ABL tyrosine kinase , on CML in blast phase . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
PURPOSE OF REVIEW : The total number of leukemia cells in the body is reduced very substantially in patients with BCR ABL positive chronic myeloid leukemia ( CML ) responding to imatinib . ^^^ Most patients with newly diagnosed chronic phase CML who receive imatinib achieve complete cytogenetic remission ( CCYR ) and low levels of BCR ABL transcripts , a status that seems to predict for relatively long survival compared with previous treatments . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Identification of mcl 1 as a BCR / ABL dependent target in chronic myeloid leukemia ( CML ) : evidence for cooperative antileukemic effects of imatinib and mcl 1 antisense oligonucleotides . ^^^ Antiapoptotic members of the bcl 2 family have recently been implicated in the pathogenesis of chronic myeloid leukemia ( CML ) , a hematopoietic neoplasm associated with the BCR / ABL oncogene . ^^^ We have examined expression of MCL 1 in primary CML cells and BCR / ABL transformed cell lines . ^^^ Together , our data identify MCL 1 as a BCR / ABL dependent survival factor and interesting target in CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Imatinib also inhibits the c abl , platelet derived growth factor ( PDGF ) receptor , abl related gene ( ARG ) and stem cell factor ( SCF ) receptor tyrosine kinases , and has been used clinically to inhibit the growth of malignant cells in patients with CML and gastrointestinal stromal tumors ( GISTs ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Imatinib mesylate is highly effective in newly diagnosed chronic myeloid leukemia ( CML ) , but BCR / ABL ( breakpoint cluster region / abelson murine leukemia ) positive progenitors persist in most patients with CML treated with imatinib mesylate , indicating the need for novel therapeutic approaches . ^^^ In mice with the CML like disease , PD 166326 rapidly inhibited Bcr / Abl kinase activity after a single oral dose and demonstrated marked antileukemic activity in vivo . ^^^ PD 166326 also prolonged the survival of mice with imatinib mesylate resistant CML induced by the Bcr / Abl mutants P210 / H396P and P210 / M351T . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Quantitative RT PCR of Wilms tumor gene transcripts ( WT 1 ) for the molecular monitoring of patients with accelerated phase bcr / abl + CML . ^^^ We investigated Wilms tumor gene ( WT 1 ) and bcr / abl mRNA transcripts in 16 accelerated phase CML patients by quantitative real time PCR . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The mechanism underlying p 210 ( BCR / ABL ) oncoprotein mediated transformation in chronic myelogenous leukemia ( CML ) is not fully understood . ^^^ We hypothesized that p 210 ( BCR / ABL ) suppresses expression of genes which may explain at least some of the pathogenetic features of CML . ^^^ We have confirmed for eight of these genes that expression was suppressed by quantitative real time RT PCR ( Q RT PCR ) of additional p 210 ( BCR / ABL ) transduced CD34+ UCB cells as well as primary early chronic phase ( CP ) bone marrow ( BM ) CML CD34+ cells . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We performed chromosome analysis on the bone marrow of a patient with BCR / ABL negative chronic myelogenous leukemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The implications of these results , and the potential role this and other novel ABL inhibitors may have in treating patients with CML , are discussed . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The BCR / ABL tyrosine kinase inhibitor imatinib has shown remarkable efficacy in treating patients with chronic myelogenous leukemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Surprisingly , the oncogenic form of c Abl , the Bcr Abl fusion protein in CML cells , also promotes the accumulation of wt p 53 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
PURPOSE : Point mutations within the ABL kinase domain of the BCR ABL gene have been associated with clinical resistance to imatinib mesylate in chronic myeloid leukemia ( CML ) patients . ^^^ To shed further light on the frequency , distribution , and prognostic significance of ABL mutations , we retrospectively analyzed a homogeneous cohort of late chronic phase CML patients who showed primary cytogenetic resistance to imatinib . ^^^ PATIENTS AND METHODS : Using denaturing high performance liquid chromatography ( D HPLC ) and sequencing , we screened for ABL mutations in a total of 178 bone marrow and / or peripheral blood samples from 40 late chronic phase CML patients homogeneously treated with imatinib 400 mg / d , who did not reach a major cytogenetic response at 12 months . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Imatinib , a Bcr Abl tyrosine kinase inhibitor , is a highly effective therapy for patients with chronic myelogenous leukemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In vitro sensitivity to imatinib induced inhibition of ABL kinase activity is predictive of molecular response in patients with de novo CML . ^^^ These data provide strong evidence that intrinsic sensitivity to imatinib is variable in previously untreated patients with CML , and the actual level of BCR ABL kinase inhibition achieved is critical to imatinib response . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The oncogenic mutations ( s ) in classic MPD are unknown except for CML , which is associated with an activating mutation ( Bcr / Abl ) of the gene encoding for the Abl cytoplasmic protein kinase ( PTK ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The clinical success of the ABL tyrosine kinase inhibitor imatinib in chronic myeloid leukaemia ( CML ) serves as a model for molecularly targeted therapy of cancer , but at least two critical questions remain . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Gleevec , which is an inhibitor of the bcr / abl tyrosine kinase , has been a remarkable success for the treatment of chronic myelogenous leukemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Imatinib mesylate is a small molecule inhibitor of the c Abl , platelet derived growth factor ( PDGF ) receptor and c Kit tyrosine kinases that is approved for the treatment of Philadelphia chromosome positive chronic myeloid leukemia ( CML ) and gastrointestinal stromal tumors . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
This agent has demonstrated considerable activity in chronic myeloid leukaemia ( CML ) by inhibiting the BCR ABL fusion protein and gastrointestinal stromal tumours ( GISTs ) , which are predominantly driven by activating mutations in KIT . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
CONCLUSION : As opposed to recent reports for c ABL , we do not see evidence for a functional interaction between BCR ABL and hTERT in this model system arguing against imatinib mediated upregulation of hTERT as a crucial factor for clonal selection and disease progression of CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Additionally , the protein acrylamide copolymer arrays detected CML cell levels as low as 15 % in a background of Bcr Abl leukemic cells and provided the framework for the parallel evaluation of six tyrosine kinase inhibitors . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Although Rb is known to be an upstream negative regulator of Abl protein tyrosine kinase , we propose here that Rb also functions as a downstream effector of Abl that plays a positive role in survival of Abl dependent human tumor cells , including Bcr / Abl positive chronic myelogenous leukemia ( CML ) . ^^^ Thus , our findings suggest that Abl catalysed tyrosine phosphorylation of Rb is necessary for survival of Abl dependent human tumor cells , and raises the possibility that this phosphorylated Rb can be a molecular target for cancer therapy aimed at inducing apoptosis of Abl dependent tumor cells , such as Bcr / Abl positive CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The constitutively activated Abl tyrosine kinase domain of the chimeric Bcr Abl oncoprotein is responsible for the transformation of haematopoietic stem cells and the symptoms of chronic myeloid leukaemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BCR / ABL fusion gene , encoding a paradigmatic tyrosine kinase involved in chronic myelogenous leukemia ( CML ) , can modulate the expression of genes involved in natural killer ( NK ) cell target recognition . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Therapy with the BCR / ABL targeting drug Imatinib ( STI 571 ) resulted in complete cytogenetic remission of CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Moreover , to the best of our knowledge , del ( 9 ) ( q 21 ) resulting in missing of a restrict region including normal ABL gene has not been found among CML cell lines previously described . ^^^ Thus , TCC S cells with only BCR / ABL gene and no normal ABL gene may be a useful tool for functional study of ABL in Ph+ CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Here , we demonstrate that IM treatment activated the phosphatidylinositol 3 kinase ( PI3K ) / Akt / mammalian target of rapamycin ( mTor ) pathway in BCR / ABL positive LAMA cells and primary leukemia cells in vitro , as well as in a chronic phase CML patient in vivo . ^^^ In contrast , IM resistant chronic myeloid leukemia ( CML ) patients with BCR / ABL kinase mutations ( n=15 ) , and IM refractory BCR / ABL positive acute lymphatic leukemia patients ( n=2 ) displayed inconsistent and kinase mutation independent autonomous patterns of Akt pathway activation , and mTor inhibition overcame IM resistance only if Akt was strongly activated . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic myeloic leukemia ( CML ) is a malignant disease of hematopoietic stem cell characterized by the bcr / abl gene rearrangement . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
OBJECTIVE : BCR / ABL fusion tyrosine kinase is responsible for the initiation and maintenance of the Philadelphia chromosome positive chronic myelogenous leukemia ( CML ) and a cohort of acute lymphocytic leukemias . ^^^ We show that a signaling protein , phosphatidylinositol 3 kinase ( PI 3k ) , is essential for growth of CML cells , but not of normal hematopoietic cells , and that p85alpha subunit of PI 3k co immunoprecipitates with BCR / ABL . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Resistance to imatinib during the treatment of chronic myeloid leukaemia ( CML ) is frequently associated with point mutations in the ABL gene encoding the ATP binding region likely to cause disease relapse . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic myeloid leukemia ( CML ) is a myeloproliferative disease in which BCR / ABL enhances survival of leukemic cells through modulation of proapoptotic and antiapoptotic molecules . ^^^ The BCR / ABL inhibitors imatinib and AMN 107 were found to promote expression of Bim in CML cells . ^^^ In summary , our data identify BCR / ABL as a Bim suppressor in CML cells and suggest that reexpression of Bim by novel tyrosine kinase inhibitors , proteasome inhibition , or by targeting signaling pathways downstream of BCR / ABL may be an attractive therapeutic approach in imatinib resistant CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The Bcr Abl inhibitor imatinib mesylate induces complete hematologic and cytogenetic remissions in most newly diagnosed chronic myeloid leukemia ( CML ) patients , but relatively few of them achieve molecular remission . ^^^ The challenge for the future is to improve current clinical results with kinase inhibitors in CML , developing strategies that can eradicate residual disease and overcome or prevent resistance . ' Dual ' Src and Abl kinase inhibitors are an attractive class of compounds , since ( a ) these molecules are able to bind Bcr Abl with less stringent conformational requirements with respect to imatinib , therefore allowing for efficient inhibition of several , resistance associated mutant forms of Bcr Abl ; ( b ) Src kinases have been shown to be involved in Bcr Abl mediated leukemogenesis as well as upregulated in some patients resistant to imatinib . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The unique fusion gene product translated , p 210 ( Bcr Abl ) , is a constitutively active tyrosine kinase that is specific to , and has a central role in the pathogenesis of , CML , making it an atractive target for drug therapy . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
CONCLUSIONS : Our results indicate that Src / Abl inhibitors are compatible with imatinib and suggest that combined Abl inhibitor therapy is a feasible treatment strategy for patients with CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic myeloid leukemia ( CML ) is characterized by the Philadelphia translocation t ( 9 ; 22 ) ( q 34 ; q 11 ) resulting in the BCR / ABL fusion gene . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Imatinib mesylate ( Gleevec ) was developed as the first molecularly targeted therapy that specifically inhibits the BCR ABL tyrosine kinase activity in patients with Philadelphia chromosome positive ( Ph+ ) chronic myeloid leukemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic myelogenous leukemia ( CML ) is characterized by the Philadelphia ( Ph ) chromosome and bcr / abl gene rearrangement which occurs in pluripotent hematopoietic progenitor cells expressing the c kit receptor tyrosine kinase ( KIT ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The archetype of this class of hematological diseases is chronic myeloid leukemia ( CML ) , characterized by the presence of the Philadelphia ( Ph ) chromosome , the result of t ( 9 ; 22 ) ( q 34 ; q 11 ) , and the associated BCR ABL 1 oncogene . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
BCR ABL nuclear entrapment kills human CML cells : ex vivo study on 35 patients with the combination of imatinib mesylate and leptomycin B . ^^^ The BCR ABL oncoprotein of chronic myelogenous leukemia ( CML ) localizes to the cell cytoplasm , where it activates proliferative and antiapoptotic signaling pathways . ^^^ Our results indicate that strategies aimed at the nuclear entrapment of BCR ABL efficiently kill human leukemic cells , suggesting that the clinical development of this approach could be of significant therapeutic value for newly diagnosed and IM resistant CML patients . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In August 2002 , he was diagnosed with CML with a peripheral white blood count of 69 , 940 / microl and positivity for Philadelphia chromosome and BCR / ABL fusion gene on bone marrow aspiration . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Selective inhibition of the BCR / ABL tyrosine kinase by imatinib has become a first line therapy for chronic myelogenous leukemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The tumor suppressor PP2A is functionally inactivated in blast crisis CML through the inhibitory activity of the BCR / ABL regulated SET protein . ^^^ The oncogenic BCR / ABL kinase activity induces and maintains chronic myelogenous leukemia ( CML ) . ^^^ We show here that , in BCR / ABL transformed cells and CML blast crisis ( CML BC ) progenitors , the phosphatase activity of the tumor suppressor PP2A is inhibited by the BCR / ABL induced expression of the PP2A inhibitor SET . ^^^ In imatinib sensitive and resistant ( T315I included ) BCR / ABL+ cell lines and CML BC progenitors , molecular and / or pharmacological activation of PP2A promotes dephosphorylation of key regulators of cell proliferation and survival , suppresses BCR / ABL activity , and induces BCR / ABL degradation . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Altered mRNA translation is one of the effects exerted by the BCR / ABL oncoprotein in the blast crisis phase of chronic myelogenous leukemia ( CML ) . ^^^ Here , we report that in BCR / ABL+ cell lines and in patient derived CML blast crisis mononuclear and CD34+ cells , p 210 ( BCR / ABL ) increases expression and activity of the transcriptional inducer and translational regulator heterogeneous nuclear ribonucleoprotein K ( hnRNP K or HNRPK ) in a dose and kinase dependent manner through the activation of the MAPK ( ERK1 / 2 ) pathway . ^^^ Furthermore , HNRPK down regulation and interference with HNRPK translation but not transcription regulatory activity impairs cytokine independent proliferation , clonogenic potential , and in vivo leukemogenic activity of BCR / ABL expressing myeloid 32Dcl3 and / or primary CD34+ CML BC patient cells . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Imatinib mesylate ( STI 571 ) , a specific inhibitor of BCR / ABL tyrosine kinase , exhibits potent antileukemic effects in the treatment of chronic myelogenous leukemia ( CML ) . ^^^ BCR / ABL positive human K 562 CML cells resistant to doxorubicin ( K562DoxR ) and their sensitive counterparts ( K562DoxS ) were used to determine the mechanism by which the STI 571 inhibitor may overcome drug resistance . ^^^ We provide evidence that treatment of CML derived BCR / ABL expressing leukemia K 562 cells with STI 571 results in the inhibition of DNA repair and abrogation of the resistance of these cells to doxorubicin . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The present study aimed to determine whether the survival of patients with CMML differs from that of patients with BCR / ABL negative CML or Ph ( 1 ) , BCR / ABL unknown CML , once other potentially prognostic variables have been accounted for . ^^^ The records of 485 patients with myeloproliferative / myelodysplastic disorders [ CMML , n = 304 ; BCR / ABL negative CML , n = 107 ; Ph ( 1 ) , BCR / ABL unknown , n = 74 ] were analysed . ^^^ The diagnosis of CMML is prognostically significant and independently associated with a shorter survival and a higher risk of death than BCR / ABL negative CML or Ph ( 1 ) BCR / ABL unknown CML . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Because expression of CEBPB ( and CEBPA ) is low in the blast crisis ( BC ) stage of chronic myelogenous leukemia ( CML ) and is inversely correlated with BCR / ABL tyrosine kinase levels , these findings point to the therapeutic potential of restoring C / EBP activity in CML BC and , perhaps , other types of acute leukemia . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
A novel C3G isoform , designated p87C3G , lacking the most amino terminal region of the cognate protein has been found to be overexpressed in two CML cell lines , K 562 and Boff 210 , both expressing Bcr Abl p 210 . p87C3G expression is also highly augmented in patients diagnosed with chronic myeloid leukemia ( CML ) Ph+ , in comparison with healthy individuals , and returns to basal levels after treatment with STI 571 . p87C3G co immunoprecipitates with both CrkL and Bcr Abl in CML cell lines and co immunoprecipitation between p87C3G and Bcr Abl was also detected in primary cells from CML patients . ^^^ These results indicate that p87C3G overexpression is linked to CML phenotype and that p87C3G may exert productive functional interactions with Bcr Abl signaling components suggesting the implication of this C3G isoform in the pathogenesis of chronic myeloid leukemia . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Finally , activation of c abl in chronic myelogenous leukaemia ( CML ) and acute lymphoblastic leukaemia could also be presented as an example , which provides probably the strongest evidence for the role of proto oncogenes in human malignancy process . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The F and G actin binding region of the BCR / ABL C terminus may be important in BCR / ABL mediated events , and we have investigated this by expressing a C terminus deletion mutant of the temperature sensitive BCR / ABL PTK , in a haemopoietic progenitor cell line , which models the chronic phase of CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The Bcr Abl fusion kinase drives oncogenesis in chronic myeloid leukemia ( CML ) . ^^^ CML patients are currently treated with the Abl tyrosine kinase inhibitor imatinib , which is effective in early stages of the disease . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
A negative correlation was found between relative levels of PDCD 5 and BCR / ABL expression in all CML patients and in CML patients in the advanced phase . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Extra BCR / ABL fusion mosaicism in 18p in a CML Ph positive patient with erythroblastic transformation . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In the present study , 79 BCR / ABL transcript positive samples from CML patients who were being monitored for minimal residual disease by real time quantitative RT PCR were studied to determine whether the 2 DeltaDeltaCt approach was equivalent to the plasmid standard curve method . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
We evaluated the potential for early minimal residual disease ( MRD ) BCR ABL quantification to predict relapse of CML patients receiving allogeneic SCT . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Dasatinib [ BMS 354825 ] is an orally active , small molecule , dual inhibitor of both SRC and ABL kinases that is under development with Bristol Myers Squibb for the treatment of patients with chronic myelogenous leukaemia ( CML ) and imatinib acquired resistance / intolerance . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
In advanced phase chronic myeloid leukemia ( CML ) , resistance to imatinib mesylate is associated with point mutations in the BCR ABL kinase domain . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The BCR / ABL gene fusion , the hallmark of chronic myelogenous leukemia ( CML ) is generated in 2 10 % of patients by a variant Ph translocation involving 9q34 , 22q11 . 2 , and one or more additional genomic regions . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Three of the most promising antigens for immunotherapy of chronic myelogenous leukaemia ( CML ) include the specific fusion protein , Bcr / Abl , and the overexpressed proteins WT 1 and Proteinase 3 . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Here , we report on a novel and complex Ph chromosome negative CML case with a t ( 6 ; 9 ) ( p 21 ; q34 . 1 ) in which the BCR / ABL fusion gene is located at 6p21 . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The emergence of ABL point mutations is the most frequent cause for imatinib resistance in chronic myelogenous leukemia ( CML ) patients and can occur during any phase of the disease ; however , their clinical impact remains controversial . ^^^ In this study , we retrospectively analyzed the predictive impact of 94 BCR ABL kinase domain mutations ( 18 T315I , 26 P loop , 50 in other sites ) found in 89 imatinib resistant CML patients . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Monitoring breakpoint cluster region Abelson kinase ( BCR ABL ) levels in patients treated for chronic myelogenous leukemia ( CML ) has become an integral part of patient management . ^^^ In this study , we compared nine commonly used control genes for three criteria : mRNA abundance , levels in CML and non CML cells , and their degradation kinetics in comparison with BCR ABL . ^^^ Although ABL is most widely used , our data suggest that the amount of ABL is different in CML and non CML cells . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Patients with CML in blast crisis ( CML BC ) became rapidly resistant to therapy with the breakpoint cluster region Abelson murine leukemia ( BCR / ABL ) kinase inhibitor imatinib ( STI 571 ) because of mutations in the kinase domain that interfere with drug binding . ^^^ Activation of C / EBPalpha in blast cells from 4 patients with CML BC , including one resistant to STI 571 and BMS 354825 and carrying the T315I Abl kinase domain mutation , also induced granulocyte differentiation . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Expression of the BCR ABL oncoprotein is sufficient and necessary for the development of a CML phenotype . ^^^ Additional BCR ABL independent chromosomal abnormalities are common in advanced phase CML and result in resistance to imatinib . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Conventional cytogenetics and FISH in the detection of BCR / ABL fusion in chronic myeloid leukemia ( CML ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic myeloid leukemia ( CML ) is a myeloproliferative disorder characterized by an abnormal fusion gene BCR ABL . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Cytogenetically , the Philadelphia ( Ph ) chromosome was found in 44 patients ( 93 . 6 % ) ; of the remaining 3 patients with Ph negative CML , 2 exhibited BCR / ABL transcripts but no BCR / ABL FISH fusion signals , suggesting the existence of two clones , with and without the BCR / ABL fusion gene . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Recently , imatinib , the BCR / ABL antagonist , took over the first choice drug of the treatment CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
This fusion protein constitutively activate ABL tyrosine kinase and causes CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
Chronic myeloid leukemia ( CML ) develops when a hematopoietic stem cell acquires the Philadelphia chromosome carrying the BCR / ABL fusion gene . ^^^ In this work , we used locked nucleic acid ( LNA ) modified oligonucleotides to silence BCR / ABL and reduce CML cell proliferation , as these oligonucleotides are resistant to nucleases and exhibit an exceptional affinity for cognate RNA . ^^^ The treatment of CML cells with junction specific antisense gapmers resulted in a strong and specific reduction of the levels of BCR / ABL transcripts ( approximately 20 % of control ) and protein p 210 ( BCR / ABL ) ( approximately 30 % of control ) . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The Philadelphia translocation t ( 9 ; 22 ) resulting in the bcr / abl fusion gene is the pathogenic principle of almost 95 % of human chronic myelogenous leukemia ( CML ) . ^^^ Imatinib mesylate ( STI 571 ) is a specific inhibitor of the BCR / ABL fusion tyrosine kinase that exhibits potent antileukemic effects in CML . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The deregulated kinase activity of p 210 BCR / ABL oncoproteins , hallmark of chronic myelogenous leukaemia ( CML ) , induces and sustains the leukaemic phenotype , and contributes to disease progression . ^^^ Imatinib mesylate , a BCR / ABL kinase inhibitor , is effective in most of chronic phase CML patients . ^^^ Thus , the combination of PP2A phosphatase activating and BCR / ABL kinase inhibiting drugs may represent a powerful therapeutic strategy for blast crisis CML patients . . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
The chromosomal translocation that fuses the phl gene with the c abl proto oncogene appears to be a pivotal step in the pathogenesis of some leukemias . ^^^
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
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Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
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Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
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Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
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Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
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Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
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Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
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Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
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Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
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Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
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Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
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Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
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Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
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Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
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Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
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Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
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Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
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Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
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Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
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Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
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Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
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Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
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Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
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Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
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Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
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Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
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Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
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Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
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Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
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Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
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Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
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Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
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Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
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Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
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Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
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Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
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Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
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Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA
Interacting proteins: P11274 and P00519	Pubmed	SVM Score :0.0
NA