Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.52949289
The ETO domain is necessary for the developmental abnormalities associated with AML 1 ETO expression in the hematopoietic stem cell compartment in vivo . 0.52949289^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.70127263
Since neither ETO nor AML 1 ETO are typically expressed in hematopoietic progenitors , we hypothesize that it is the interactions between AML 1 ETO and regulatory cofactors in disease state cells that alter gene expression programs during hematopoiesis . 0.70127263^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.52815875
CBFA 2 forms a fusion gene with ETO and MDS1 / EVI1 in translocations in myeloid leukemia and with ETV 6 ( TEL ) in the t ( 12 ; 21 ) common in childhood pre B acute lymphoblastic leukemia . 0.52815875^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The base composition of one of the additional products was determined and was found to contain a new 68 bp ETO sequence present at the fusion of AML 1 and ETO genes . ^^^ Molecular diversity in the AML 1 ETO transcripts will have consequences for the detection of minimal residual disease and antisense studies . . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
Recently , two genes AML 1 , which has a unique runt domain , and ETO ( MTG 8 ) have been isolated from the chromosomal breakpoint . ^^^ AML 1 and ETO were fused at the same position in these transcripts . ^^^ The widespread expression of AML 1 and ETO in hematopoietic cells suggests a fundamental role of these proteins in hematopoiesis . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The ETO sequence is different from the portion of PEBP 2 alpha B it replaces in the AML1 / ETO fusion protein , except for their common high content of proline , serine , and threonine residues . ^^^ Because neither the putative zinc fingers nor the TAF 110 homology domain of ETO is present in PEBP 2 alpha B , one might expect functional differences in the ability of AML1 / ETO protein to affect the levels of transcription of genes normally regulated to some degree by AML 1 ( PEBP 2 alpha B ) during myeloid differentiation . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
A common chromosomal translocation in acute myeloid leukemia ( AML ) involves the AML 1 ( acute myeloid leukemia 1 , also called RUNX 1 , core binding factor protein ( CBF alpha ) , and PEBP 2 alpha B ) gene on chromosome 21 and the ETO ( eight twenty one , also called MTG 8 ) gene on chromosome 8 . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The critical consequence of the translocation is the juxtaposition of 5 ' sequences of AML 1 to 3 ' sequences of ETO , oriented telomere to centromere on the der ( 8 ) chromosome . . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
Functional domains of the t ( 8 ; 21 ) fusion protein , AML 1 / ETO . ^^^ The AML 1 / ETO fusion protein is created by the ( 8 ; 21 ) translocation , the second most frequent chromosomal abnormality associated with acute myeloid leukemia . ^^^ In the fusion protein the AML 1 runt homology domain , which is responsible for DNA binding and CBF beta interaction , is linked to ETO , a gene of unknown function . ^^^ Mutagenesis of AML 1 / ETO was performed to delimit the functional domains of the chimeric protein . ^^^ C terminal deletion mutants of AML 1 / ETO indicated that ETO sequences are essential for interference with AML 1B mediated transcriptional activation , and that residue 540 defines the C terminal boundary of a potential repression domain . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
In all samples , the size of the amplified DNA fragments and pattern of restriction digest were identical , indicating that the t ( 8 ; 21 ) translocation breakpoint occurs within a single intron of the AML 1 and ETO genes . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The 8 ; 21 chromosomal translocation involves the AML 1 gene on chromosome 21 and the ETO gene on chromosome 8 and results in the transcription of a chimeric message . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
It is likely that alterations of AML 1 or MTG 8 gene and p 53 gene contribute to a disease progression in this case . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The AML 1 and ETO genes in acute myeloid leukemia with a t ( 8 ; 21 ) . ^^^ The breakpoints in this translocation have been characterized at the molecular level , and the genes involved are AML 1 on chromosome 21 and ETO ( eight twenty one ) on chromosome 8 . ^^^ Both AML 1 and ETO are thought to be transcription factors because the motifs they contain are found in other transcription factors . ^^^ The rearrangement between the two chromosomes results in a fusion gene that contains the 5 ' region of AML 1 including that homologous to runt fused to almost all of ETO . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
BACKGROUND . t ( 8 ; 21 ) ( q 22 ; q 22 ) , found in acute myeloid leukemia ( AML ) and occasionally in myelodysplasia ( MDS ) , results in the fusion of the AML 1 gene on 22q22 to the ETO gene on 8q22 , generating a chimeric AML1 / ETO transcript , which is a molecular marker of the translocation . ^^^ Reverse transcription polymerase chain reaction ( RT PCR ) , with two pairs of nested AML 1 and ETO primers , was used to amplify the AML1 / ETO fusion transcript . ^^^ Using this approach , patients with t ( 8 ; 21 ) ( three patients with de novo AML , one with therapy related AML , and one patient with myelodysplasia ) yielded the same 222 base pair PCR product , suggesting that the breakpoints occurred at the same AML 1 and ETO introns as previously reported . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
In eight cases we used FISH with AML 1 cosmid probes on metaphase chromosomes as well as RT PCR to detect the junctions of MAL1 / CDR ( ETO , MTG 8 ) . ^^^ This transcript showed splicing of AML 1 exon 5 onto CDR . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
At the molecular level the translocation results in the fusion of the 5 ' region of the AML 1 gene on chromosome 21 and almost the entire CDR gene ( also ETO or MTG 8 ) on chromosome 8 . ^^^ To detect the translocation at the single cell level , we used two probes , a cosmid clone containing the first five exons of AML 1 and a P 1 clone containing the entire CDR gene . ^^^ Simultaneous hybridization of the CDR and AML 1 probes to interphase cells resulted in one red and one green hybridization signal randomly located in the cell , from the hybridization to the normal chromosomes ( 8 , 21 ) , and one red green pair of signals from the close hybridization of the two probes to the fusion gene on the derivative 8q chromosome , indicating the translocation . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The t ( 8 ; 21 ) translocation fuses the first 177 amino acids of AML 1 to MTG 8 ( also known as ETO ) , generating a chimeric protein that retains the DNA binding domain of AML 1 . ^^^ Subcellular fractionation experiments demonstrated that both AML 1 and AML 1 / ETO are efficiently extracted from the nucleus under ionic conditions but that AML 1B is localized to a salt resistant nuclear compartment . ^^^ Analysis of the transcriptional activities of AML 1 , AML 1B , and AML 1 / ETO demonstrated that only AML 1B activates transcription from the T cell receptor beta enhancer . ^^^ Mixing experiments indicated that AML 1 / ETO can efficiently block AML 1B dependent transcriptional activation , suggesting that the t ( 8 ; 21 ) translocation creates a dominant interfering protein . . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
Recently , breakpoint region genes for the 8 ; 21 translocation in chromosome 8 and 21 have been isolated , 48 50 and have been named AML 1 and ETO , respectively . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The t ( 8 ; 21 ) translocation is one of the most frequent chromosomal abnormalities in acute myeloid leukaemia and results in gene fusion between AML 1 on chromosome 21 and MTG 8 ( = ETO or CDR ) on chromosome 8 . ^^^ The rearrangement occurs within a specific intron of the AML 1 gene and results in the formation of a chimaeric protein with the consistent feature that the region of sequence homology of AML 1 is fused with almost the entire MTG 8 protein . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
These results suggest that previously described chimeric gene products , AML1 / MTG8 ( ETO ) and AML 1 EAP generated by t ( 8 ; 21 ) and t ( 3 ; 21 ) , respectively , lack the transactivation domain of AML1 . . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The genes rearranged by t ( 8 ; 21 ) , named AML 1 on 21 and ETO on 8 , were recently identified . ^^^ AML 1 shows homology with the Drosophila segmentation gene runt and ETO with cyclin D 2 . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
Here we report that this translocation juxtaposes the AML 1 gene with a novel gene , named MTG 8 , on chromosome 8 , resulting in the synthesis of an AML 1 MTG8 fusion transcript . ^^^ The fusion protein predicted by the AML 1 MTG8 transcript consists of the runt homology region of AML 1 and the most part of MTG 8 , which contains putative zinc finger DNA binding motifs and proline rich regions constituting a characteristic feature of transcription factors . ^^^ The MTG 8 gene is not expressed in normal hematopoietic cells , whereas AML 1 is expressed at high levels . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The breakpoints in this translocation have been characterized at the molecular level , and the genes involved are AML 1 on chromosome 21 and ETO on chromosome 8 . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The analysis of the cDNAs structure has led to the identification of the fusion of AML 1 with a gene named MTG 8 on chromosome 8 , which seems to be identical to ETO . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
In the 8 ; 21 translocation , the AML 1 gene , located at chromosome band 21q22 , is translocated to chromosome 8 ( q 22 ) , where it is fused to the ETO gene and transcribed as a chimeric gene . ^^^ The fusion clone contains the DNA binding 5 ' part of AML 1 that is fused to ETO in the t ( 8 ; 21 ) and , in addition , at least one other exon . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
Detection of DNA rearrangements in the AML 1 and ETO loci and of an AML1 / ETO fusion mRNA in patients with t ( 8 ; 21 ) acute myeloid leukemia . ^^^ The translocation interrupts two genes , AML 1 on chromosome 21 and ETO on chromosome 8 , that are consequently fused in the der ( 8 ) chromosome to produce a novel chimeric gene and message . ^^^ We also used the polymerase chain reaction ( PCR ) with appropriate primers from the AML 1 and ETO genes to amplify the cDNAs from a cell line with the t ( 8 ; 21 ) and from seven AML patients with the t ( 8 ; 21 ) . ^^^ These results indicate that , whereas several DNA probes used as genetic markers do detect the t ( 8 ; 21 ) in most , but not all Southern blots of patients with AML , PCR amplification with primers from AML 1 and ETO can be used as a more sensitive and accurate means for detecting this chromosomal abnormality , and for observing the patients ' response to therapy . . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
Expression of AML 1 ETO fusion transcripts and detection of minimal residual disease in t ( 8 ; 21 ) positive acute myeloid leukemia . ^^^ Sequence analysis of the amplified DNA fragments demonstrated that all fusion transcripts were fused at exactly the same site , indicating that this translocation breakpoint occurs within a single intron of the AML 1 and ETO genes . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
This gene on the 8q derivative represents the fusion between the 5 ' portion of the AML 1 gene with the 3 ' portion of a chromosome 8 gene that contains a region of sequence homology with the cyclin D 2 gene , here referred to as the CDR gene ( cyclin D related gene ) . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The AML 1 gene is transcribed from telomere to centromere , and in the t ( 8 ; 21 ) the 5 ' part of AML 1 is fused to the ETO gene on chromosome 8 to produce the chimeric AML1 / ETO on the der ( 8 ) chromosome . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The chromosomal breakpoints have recently been identified at the molecular level and shown to involve the AML 1 gene on chromosome 21 and the ETO gene on chromosome 8 . ^^^ Using oligonucleotide primers derived from the AML 1 and ETO cDNAs , we were able to amplify a specific fusion transcript from 26 of 26 patients with t ( 8 ; 21 ) by a reverse transcriptase polymerase chain reaction ( PCR ) approach . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The t ( 8 ; 21 ) translocation , commonly found in acute myelogenous leukemia ( AML ) , generates a fusion protein containing N terminal AML 1 and C terminal ETO amino acids . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
In the t ( 8 ; 21 ) acute myelogenous leukemia ( AML ) , AML 1 was found fused to a gene on chromosome 8 that we designated CDR ( also known as ETO and MTG 8 ) . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The t ( 8 ; 21 ) ( q 22 ; q 22 ) interrupts AML 1 after the runt homology domain , and fuses the 5 ' part of AML 1 to almost all of ETO , the partner gene on chromosome 8 . ^^^ AML 1 is an activator of several myeloid promoters ; however , the chimeric AML1 / ETO is a strong repressor of some AML 1 dependent promoters . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
One ribozyme , A / MRZ 1 , recognizes the area adjacent to the fusion point between AML 1 and MTG 8 , and cleaves six bases downstream from this point . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
It is associated predominantly , but not exclusively , with AML M 2 , and corresponds to rearrangements involving the AML 1 and ETO genes . ^^^ AML 1 ETO positive , t ( 8 ; 21 ) negative cases are well recognized but their incidence is unknown . ^^^ In order to determine optimal prospective AML 1 ETO RT PCR screening strategies , we analysed 64 unselected AML M 1 and M 2 cases and correlated the results with other biological parameters . ^^^ AML 1 ETO was found in 3 % ( 1 / 32 ) of AML M 1 and 25 % ( 8 / 32 ) of M 2 , including three patients without a classic ( 8 ; 21 ) but with chromosome 8 abnormalities . ^^^ Correlation with morphology enabled development of a scoring system which detected all nine AML 1 ETO positive cases with a false positive rate of 7 % ( 4 / 55 ) . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
Translocation ( 8 ; 21 ) ( q 22 ; q 22 ) involves fusion of the AML 1 gene with the ETO gene , generating an AML1 / ETO fusion transcript that can be detected by the polymerase chain reaction ( PCR ) . ^^^ Persistence of the AML1 / ETO transcript has been demonstrated by PCR in patients with t ( 8 ; 21 ) in long term remission , but the rearranged AML 1 gene could not be detected by Southern analysis , showing that the t ( 8 ; 21 ) clone existed as minimal residual disease ( MRD ) . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
This translocation interrupts two genes , AML 1 on chromosome 21q and MTG 8 ( ETO ) on 8q to form a chimeric gene AML1 / MTG8 on the der ( 8 ) chromosome . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
ETO and AML 1 phosphoproteins are expressed in CD34+ hematopoietic progenitors : implications for t ( 8 ; 21 ) leukemogenesis and monitoring residual disease . ^^^ To study acute myelogenous leukemia 1 ( AML 1 ) transcription factor , ETO protein , and t ( 8 ; 21 ) AML chimeric AML1 / ETO protein in normal hematopoiesis and in leukemia , we raised rabbit antisera to a bacterially expressed polypeptide containing amino acid residues 1 to 220 of ETO and to synthetic peptides extending from residues 528 to 548 of ETO and 32 to 50 of AML 1 . ^^^ With affinity purified reagents , we observed immunofluorescent staining for both AML 1 and ETO in the nucleus of HEL , K 562 , and Kasumi 1 leukemic cell lines , the last from a t ( 8 ; 21 ) AML . ^^^ Biochemical analysis confirmed specificity of the antibodies and the nuclear localization of the antigens , the latter being exclusive for AML 1 and primary for ETO . ^^^ Immunoprecipitations of metabolically labeled 32P proteins from Kasumi 1 cells show that AML 1 and ETO are phosphorylated on serine and threonine . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The t ( 8 ; 21 ) creates a fusion protein between AML 1 and a gene of unknown function , mtg 8 ( ETO ) , whereas the t ( 12 ; 21 ) fuses the TEL ( translocation ets leukemia ) transcription factor to the N terminus of AML 1 . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
AML 1 is involved in the ( 8 ; 21 ) translocation , associated with acute myelogenous leukemia ( AML ) type M 2 , which results in the production of the AML 1 ETO fusion protein : the amino terminal 177 amino acids of AML 1 and the carboxyl terminal 575 amino acids of ETO . ^^^ The mechanism by which AML 1 ETO accomplishes leukemic transformation is unknown ; however , AML 1 ETO interferes with AML 1 transactivation of such AML 1 targets as the T cell receptor beta enhancer and the granulocyte macrophage colony stimulating factor promoter . ^^^ Herein , we explored the effect of AML 1 ETO on regulation of a myeloid specific AML 1 target , the macrophage colony stimulating factor ( M CSF ) receptor promoter . ^^^ We found that AML 1 ETO and AML 1 work synergistically to transactivate the M CSF receptor promoter , thus exhibiting a different activity than previously described . ^^^ Truncation mutants within the ETO portion of AML 1 ETO revealed the region of ETO necessary for the cooperativity between AML 1 and AML 1 ETO lies between amino acids 347 and 540 . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
In t ( 8 ; 21 ) acute myelogenous leukemia ( AML ) , the AML 1 gene is juxtaposed to the ETO gene located on chromosome 8 , generating an AML1 / ETO fusion protein . ^^^ Both AML1 / ETO and the AML 1 proteins recognize the same consensus DNA binding motif ( TGT / CGGT ) , which is found in the promoters of several genes involved in hematopoiesis . ^^^ We demonstrated sequence specific binding of both AML1A and AML1 / ETO to the TGTGGT sequence in the BCL 2 promoter and showed that the AML 1 binding site is required for responsiveness to AML1 / ETO . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The translocation results in a fusion transcript between AML 1 and MTG 8 ( ETO ) , assigned on chromosomes 21 and 8 , respectively . ^^^ Acute myelogenous leukemia with ins ( 21 ; 8 ) expressing AML 1 MTG 8 fusion transcript ] . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
This translocation juxtaposes the AML 1 gene on chromosome 21 with the MTG 8 ( ETO ) gene on chromosome 8 , resulting in the expression of the AML 1 MTG8 ( ETO ) fusion transcript . ^^^ Expression of the AML 1 MTG8 ( ETO ) , bcl 2 , and c myc genes was unchanged following exposure to dexamethasone . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
Embryonic lethality and impairment of haematopoiesis in mice heterozygous for an AML 1 ETO fusion gene . ^^^ A reciprocal translocation , t ( 8 ; 21 ) ( q 22 ; q 22 ) , observed in the leukaemic cells of approximately 40 % of patients with the M 2 subtype of AML disrupts both the AML 1 ( CBFA 2 ) gene on chromosome 21 and the ETO ( MTG 8 ) gene on chromosome 8 ( refs 3 5 ) . ^^^ A chimaeric protein is synthesized from one of the derivative chromosomes that contains the N terminus of the AML 1 transcription factor , including its DNA binding domain , fused to most of ETO , a protein of unknown function . ^^^ Mice heterozygous for an AML 1 ETO allele ( AML 1 ETO / + ) die in midgestation from haemorrhaging in the central nervous system and exhibit a severe block in fetal liver haematopoiesis . ^^^ This phenotype is very similar to that resulting from homozygous disruption of the AML 1 ( Cbfa 2 ) or Cbfb genes , indicating that AML 1 ETO blocks normal AML 1 function . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
In order to design the best construct for therapeutic hammerhead ribozymes against AML 1 MTG8 , the t ( 8 ; 21 ) associated fusion mRNA of acute myeloid leukemia , we synthesized DNA / RNA chimeric ribozymes directed to the area adjacent to the fusion point between AML 1 and MTG 8 . ^^^ Catalytic efficiency and fusion gene specificity of ribozymes were examined by kinetic studies of the cleavage reactions of AML 1 MTG8 , AML 1 , and MTG 8 RNAs transcribed in vitro . ^^^ Rz4 . 3 also cleaved MTG 8 RNA but the cleavage efficiency was three orders of magnitude lower than that for AML 1 MTG8 RNA . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
Moreover , double color FISH using ETO CDR P 1 probe and a cosmid for the 5 ' part of AML 1 on chromosome 21 showed a two color signal on the 8q , suggesting a recombination between ETO and AML 1 . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
MTG 8 is a counterpart gene of AML 1 in acute myeloid leukemia with t ( 8 : 21 ) translocation . ^^^ Most of the coding region of the MTG 8 is fused with AML 1 runt domain . ^^^ MTG 8 may be important in leukemogenesis as well as in AML 1 truncation . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
Juxtaposition of the AML 1 gene on chromosome 21 to the ETO gene on chromosome 8 fuses the NH 2 terminal portion of AML 1 to near full length ETO , creating AML1 / ETO . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
In the t ( 8 ; 21 ) , AML 1 is fused to the ETO ( MTG 8 ) gene , resulting in a hybrid AML1 / ETO mRNA , which in turn is translated into a chimeric protein . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The genes PML and AML 1 , and ETO were examined in normal hematopoietic progenitors and their fusions proteins , PML / RAR alpha and AML1 / ETO , measured in patients in clinical remission , and important data were presented concerning these proteins and measurement of minimal residual disease . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
In this case the AML1 / MTG8 ( ETO ) fusion transcript was not detected by reverse transcriptase polymerase chain reaction ( RT PCR ) , and the rearrangement of the AML 1 gene locus was not detected by Southern blot nor pulse field gel electrophoresis ( PFGE ) analyses using specific probes for the AML 1 gene . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
As a consequence of the translocation the AML 1 ( CBFA 2 ) gene in the 21q22 region is fused to the ETO ( CDR , MTG 8 ) gene in the 8q22 region , resulting in one transcriptionally active gene on the 8q derivative chromosome . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The AML 1 MTG8 leukemic fusion protein forms a complex with a novel member of the MTG 8 ( ETO / CDR ) family , MTGR 1 . ^^^ In the t ( 8 ; 21 ) translocation associated with acute myeloid leukemia ( AML ) , the AML 1 ( CBFA2 / PEBP2alphaB ) gene is juxtaposed to the MTG 8 ( ETO / CDR ) gene . ^^^ Molecular cloning of cDNA indicated that the AML 1 MTG8 binding protein ( MTGR 1 ) is highly related to MTG 8 and similar to Drosophila Nervy . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
Molecular analysis of the marrow mononuclear cells by reverse transcription polymerase chain reaction with nested AML 1 and ETO primers showed amplification of the AML1 / ETO fusion transcript , thus confirming that the chromosomal aberration was in fact a masked t ( 8 ; 21 ) , i . e . , variant t ( 8 ; 20 ; 21 ) ( q 22 ; q 13 ; q 22 ) . . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The AML1 / ETO ( MTG 8 ) and AML1 / Evi 1 leukemia associated chimeric oncoproteins accumulate PEBP2beta ( CBFbeta ) in the nucleus more efficiently than wild type AML 1 . ^^^ AML 1 , a gene on chromosome 21 encoding a transcription factor , is disrupted in the ( 8 ; 21 ) ( q 22 ; q 22 ) and ( 3 ; 21 ) ( q 26 ; q 22 ) chromosomal translocations associated with myelogenous leukemias ; as a result , chimeric proteins AML1 / ETO ( MTG 8 ) and AML1 / Evi 1 are generated , respectively . ^^^ AML1 / ETO ( MTG 8 ) and AML1 / Evi 1 are nuclear proteins , as is wild type AML 1 . ^^^ Polyomavirus enhancer binding protein ( PEBP ) 2beta ( core binding factor [ CBF ] beta ) , a heterodimerizing partner of AML 1 that is located mainly in the cytoplasm , was translocated into the nucleus with dependence on the runt domain of AML1 / ETO ( MTG 8 ) or AML1 / Evi 1 when coexpressed with these chimeric proteins . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
This translocation results in the fusion of TEL , a recently described ETS like gene on 12p13 , and AML 1 , which was shown to be involved in the formation of fusion genes with ETO and EVI 1 in myeloid leukemias . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
Characterization of the ETO and AML 1 ETO proteins involved in 8 ; 21 translocation in acute myelogenous leukemia . ^^^ The AML 1 and ETO genes are disrupted by the nonrandom chromosomal translocation t ( 8 ; 21 ) in acute myelogenous leukemia ( AML ) . ^^^ While the AML 1 gene encodes a transcription factor indispensable for definitive hematopoiesis , the biological function of ETO is unknown . ^^^ To understand the role of ETO and AML 1 ETO in the pathogenesis of AML , the full length cDNAs of ETO and AML 1 ETO were cloned and antibodies against AML 1 and ETO proteins have been developed in our laboratory . ^^^ Western blot analysis showed that ETO and AML 1 ETO were identified as 70 kDa and 94 kDa proteins , respectively , and that both proteins , like AML 1 , were associated with the nuclear matrix . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The partner gene of AML 1 in t ( 16 ; 21 ) myeloid malignancies is a novel member of the MTG 8 ( ETO ) family . ^^^ The structural analysis of the cDNAs showed that AML 1 was fused to a novel gene named MTG 16 ( Myeloid Translocation Gene on chromosome 16 ) which shows high homology to MTG 8 ( ETO / CDR ) and MTGR 1 . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
In the t ( 8 ; 21 ) translocation , the AML 1 ( CBFA2 / PEBP2alphaB ) gene becomes fused to the MTG 8 ( ETO ) gene . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The t ( 8 ; 21 ) translocation associated with acute myeloid leukemia ( AML ) disrupts two genes , the AML 1 gene also known as the core binding factor A 2 ( CBFA 2 ) on chromosome 21 , and a gene on chromosome 8 , hereafter referred to as MTG 8 , but also known as CDR and ETO . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The MTG 8 ( ETO ) gene has been identified as the translocation partner of AML 1 ( PEBP2alphaB or CBFalpha 2 ) gene in the AML1 / MTG8 ( ETO ) fused gene caused by t ( 8 ; 21 ) translocation in human acute myeloid leukaemia , M 2 type . ^^^ Although AML1 / MTG8 chimaeric protein is known to inhibit the functioning of AML 1 protein , the precise function of MTG 8 gene itself is not known yet . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
This translocation fuses the AML 1 gene on chromosome 21q to the MTG 8 ( ETO ) gene on chromosome 8q to produce the fusion gene AML 1 MTG8 . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The t ( 8 ; 21 ) translocation between two genes known as AML 1 and ETO is seen in approximately 12 15 % of all acute myeloid leukemia ( AML ) and is the second most frequently observed nonrandom genetic alteration associated with AML . ^^^ AML 1 up regulates a number of target genes critical to normal hematopoiesis , whereas the AML1 / ETO fusion interferes with this trans activation . ^^^ This observation provides a mechanism for how the AML1 / ETO fusion may inhibit expression of AML 1 responsive target genes and disturb normal hematopoiesis . . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
Remarkably , all acute myeloblastic leukaemias that carried the chromosomal translocation t ( 8 ; 21 ) , which fuses the genes AML 1 and ETO , expressed PRAME at a high level . . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
It produces a chimeric protein , acute myeloid leukemia 1 ( AML 1 ) eight twenty one ( ETO ) , that contains the amino terminal DNA binding domain of the AML 1 transcriptional regulator fused to nearly all of ETO . ^^^ Finally , AML 1 / ETO associates with histone deacetylase activity and a histone deacetylase inhibitor impairs the ability of the fusion protein to repress transcription . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
We report here that ETO ( eight twenty one or MTG 8 ) , which is fused to the acute myelogenous leukemia 1 ( AML 1 ) transcription factor in t ( 8 ; 21 ) AML , interacts via its zinc finger region with a conserved domain of the corepressors N CoR and SMRT and recruits HDAC in vivo . ^^^ The fusion protein AML 1 ETO retains the ability of ETO to form stable complexes with N CoR / SMRT and HDAC . ^^^ Deletion of the ETO C terminus abolishes CoR binding and HDAC recruitment and severely impairs the ability of AML 1 ETO to inhibit differentiation of hematopoietic precursors . ^^^ These data indicate that formation of a stable complex with CoR HDAC is crucial to the activation of the leukemogenic potential of AML 1 by ETO and suggest that aberrant recruitment of corepressor complexes is a general mechanism of leukemogenesis . . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
Simple variant t ( 8 ; 21 ) acute myeloid leukemias harbor insertions of the AML 1 or ETO genes . ^^^ The locations of the breakpoints , 21q22 in patient 1 and 8q22 in patient 2 , prompted us to search for a cryptic t ( 8 ; 21 ) ( q 22 ; q 22 ) and involvement of the AML 1 and ETO genes . ^^^ However , dual color FISH using appropriate ETO and AML 1 probes disclosed an insertion of AML 1 into 8q22 on the derivative chromosome 8 in patient 1 and of ETO into 21q22 on one chromosome 21 in patient 2 , leading to AML 1 ETO fusion signals . ^^^ Both cases expressed an AML 1 ETO transcript , shown by reverse transcriptase polymerase chain reaction and cDNA sequencing . ^^^ Creation of functional AML 1 ETO fusion genes in these two simple variant t ( 8 ; 21 ) probably occurred through complex mechanisms , combining translocation and insertion of chromosomal segments . . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The translocation results in the fusion of two genes , AML 1 ( CBFA 2 ) on chromosome 21 and ETO ( MTG 8 ) on chromosome 8 . ^^^ AML 1 encodes a DNA binding factor ; the ETO protein product is less well characterized , but is thought to be a transcription factor . ^^^ This region is conserved in the oncoprotein AML 1 / ETO . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The 8 ; 21 translocation is the most common cytogenetic abnormality in human acute myelogenous leukemia , joining the AML 1 gene on chromosome 21 , to the ETO gene on chromosome 8 , forming the AML1 / ETO fusion gene . ^^^ The AMLI / ETO fusion protein has been shown to function mainly as a transcriptional repressor of AML 1 target genes and to block AML 1 function in vitro and in vivo . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The t ( 8 ; 21 ) between the AML 1 and ETO genes is a commonly seen genetic alteration in acute myeloid leukemia . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The molecular detection of the AML1 / ETO fusion gene is possible by reverse transcriptase polymerase chain reaction ( RT PCR ) or dual color fluorescence in situ hybridization ( FISH ) using probes specific for AML 1 and ETO . ^^^ Two were AML1 / ETO positive by RT PCR , one showed a rearrangement by AML 1 by Southern analysis , and the fourth had morphological features characteristic of t ( 8 ; 21 ) . ^^^ The FISH results showed a co localization of one AML 1 and one ETO signal in interphase and metaphase nuclei in all four cases , demonstrating the presence of variant t ( 8 ; 21 ) ( q 22 ; q 22 ) rearrangements . ^^^ Therefore , FISH analysis with the AML 1 and ETO probes is extremely valuable , in cases of AML M 2 , because of its ability to reveal masked t ( 8 ; 21 ) ( q 22 ; q 22 ) translocations and thus quickly confirm the diagnosis , allowing patients to be assigned to the correct risk group in terms of treatment . . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
Here we report that substitution of the chromosome 8 derived ETO protein for the multifunctional C terminus of AML 1 precludes targeting of the factor to AML 1 subnuclear domains . ^^^ Our results link the ETO chromosomal translocation in AML with modifications in the intranuclear trafficking of the key hematopoietic regulatory factor , AML 1 . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
AML 1 MTG8 fusion protein , which is produced from the rearranged gene formed between AML 1 and MTG 8 in myeloid leukemia with t ( 8 ; 21 ) chromosomal translocation , plays an important role in the pathogenesis of leukemia . ^^^ We previously showed that ectopically expressed AML 1 MTG8 fusion protein is associated with an MTG 8 like protein in the mouse myeloid precursor cell line L G , and this association seemed to be required for AML 1 MTG8 to stimulate proliferation . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The ETO protein was originally identified by its fusion to the AML 1 transcription factor in translocation ( 8 ; 21 ) associated with the M 2 form of acute myeloid leukemia ( AML ) . ^^^ The resulting AML 1 ETO fusion is an aberrant transcriptional regulator due to the ability of ETO , which does not bind DNA itself , to recruit the transcriptional corepressors N CoR , SMRT , and Sin3A and histone deacetylases . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
RAR and AML 1 transcription factors are found in leukemias as fusion proteins with PML and ETO , respectively . ^^^ Association of PML RAR and AML 1 ETO with the nuclear corepressor ( N CoR ) / histone deacetylase ( HDAC ) complex is required to block hematopoietic differentiation . ^^^ We show that PML RAR and AML 1 ETO exist in vivo within high molecular weight ( HMW ) nuclear complexes , reflecting their oligomeric state . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
In this translocation , the AML 1 ( CBFA2 / PEBP2aB ) gene is disrupted and fused to the MTG 8 ( ETO ) gene . ^^^ AML 1 MTG 8 leukemic protein induces the expression of granulocyte colony stimulating factor ( G CSF ) receptor through the up regulation of CCAAT / enhancer binding protein epsilon . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
Our results show that expression of a chimeric transcription factor encoded by the tumor related chromosomal translocation ( 8 ; 21 ) involving the AML 1 and ETO loci is sufficient to cause reorganization of PML domains . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
Ribonuclease H attack of leukaemic fused transcripts AML 1 MTG8 ( ETO ) by DNA / RNA chimeric hammerhead ribozymes . ^^^ RESULTS : To evaluate the usefulness of synthesized DNA / RNA hammerhead ribozymes targeting AML 1 MTG8 ( ETO ) leukaemic fusion transcripts in vivo , we analysed their effects on cell growth and the mechanism of action using isolated cell nuclei . ^^^ These ribozymes inhibited the growth of leukaemic cell lines expressing the AML 1 MTG 8 and degraded AML 1 MTG8 mRNA in isolated nuclei of these cells . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
In the t ( 8 ; 21 ) the AML 1 gene on chromosome 21 is fused to ETO on chromosome 8 . ^^^ The resultant hybrid protein is comprised of the DNA binding domain of AML 1 and the majority of ETO . ^^^ This study examines the subnuclear distributions of ETO , AML 1B and AML 1 / ETO proteins fused to green fluorescence protein in living cells using fluorescence microscopy . ^^^ Additionally , ETO and AML 1 / ETO co localized to punctate nuclear bodies distinct from those containing promyelocytic leukemia protein . ^^^ Thus , ETO and AML 1 / ETO reside in potentially novel subnuclear compartments . . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The N terminal portion of AML 1 , which is retained in AML1 / ETO , contains a region of homology to the FAST proteins , which cooperate with Smads to regulate transforming growth factor beta 1 ( TGF beta 1 ) target genes . ^^^ We have demonstrated the physical association of Smad proteins with AML 1 and AML1 / ETO by immunoprecipitation and have mapped the region of interaction to the runt homology domain in these AML 1 proteins . ^^^ Using confocal microscopy , we demonstrated that AML 1 , and ETO and / or AML1 / ETO , colocalize with Smads in the nucleus of t ( 8 ; 21 ) positive Kasumi 1 cells , in the presence but not the absence of TGF beta 1 . ^^^ Using transient transfection assays and a reporter gene construct that contains both Smad and AML 1 consensus binding sequences , we demonstrated that overexpression of AML1B cooperates with TGF beta 1 in stimulating reporter gene activity , whereas AML1 / ETO represses basal promoter activity and blocks the response to TGF beta 1 . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
AML 1 / ETO fusion protein is a dominant negative inhibitor of transcriptional repression by the promyelocytic leukemia zinc finger protein . ^^^ The AML 1 / ETO fusion protein , created by the ( 8 ; 21 ) translocation in M 2 type acute myelogenous leukemia ( AML ) , is a dominant repressive form of AML 1 . ^^^ This effect is due to the ability of the ETO portion of the protein to recruit co repressors to promoters of AML 1 target genes . ^^^ In transiently transfected cells and in a cell line derived from a patient with t ( 8 ; 21 ) leukemia , PLZF and AML 1 / ETO formed a tight complex . ^^^ In transient assays , AML 1 / ETO blocked transcriptional repression by PLZF , even at substoichiometric levels relative to PLZF . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
Nearly 40 % of cases of acute myelogenous leukemia ( AML ) of the M 2 subtype are due to a chromosomal translocation that combines a sequence specific DNA binding protein , AML 1 , with a potent transcriptional repressor , ETO . ^^^ ETO interacts with nuclear receptor corepressors SMRT and N CoR , which recruit histone deacetylase to the AML 1 ETO oncoprotein . ^^^ NHR 2 is also required for SMRT interaction and repression by ETO , as well as for inhibition of hematopoietic differentiation by AML 1 ETO . ^^^ NHR 2 mediates oligomerization of ETO as well as AML 1 ETO . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
In acute myeloid leukemias ( AMLs ) with t ( 8 ; 21 ) , the transcription factor AML 1 is juxtaposed to the zinc finger nuclear protein ETO ( Eight Twenty One ) , resulting in transcriptional repression of AML 1 target genes . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
ETV6 / RUNX1 ( AML 1 ) , RUNX1 / CBFA2T1 ( ETO ) , ETV6 / EVI1 , RUNX1 / EVI1 , ETV6 / ABL , BCR / ABL ) . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The t ( 8 ; 21 ) , associated with AML , results in a chimeric transcription factor , AML 1 / ETO ( eight twenty one ) , that remains attached to the nuclear matrix through targeting signals contained in the ETO protein . ^^^ When co expressed , ETO and AML 1 / ETO co localize to a nuclear compartment distinct from that of AML 1 or PML nuclear bodies . ^^^ Interestingly , enforced expression of ETO or AML 1 / ETO changes the average number of PML nuclear bodies per cell . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
It joins the 5 ' section of the AML 1 gene with the almost complete open reading frame of MTG 8 ( ETO ) . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The observation of breakpoints at 8q22 and 21q22 suggested a rearrangement of the ETO and AML 1 genes , respectively . ^^^ Using a dual color FISH test with ETO and AML 1 probes , we demonstrated an AML1 / ETO fusion signal on the derivative chromosome 8 . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
AML 1 ETO expression is directly involved in the development of acute myeloid leukemia in the presence of additional mutations . ^^^ The translocation , which involves the AML 1 gene on chromosome 21 and the ETO gene on chromosome 8 , generates an AML 1 ETO fusion transcription factor . ^^^ To examine the effect of the AML 1 ETO fusion protein on leukemogenesis , we made transgenic mice in which expression of AML 1 ETO is under the control of the human MRP 8 promoter ( hMRP 8 AML1 ETO ) . ^^^ AML 1 ETO is specifically expressed in myeloid cells , including common myeloid progenitors of hMRP 8 AML1 ETO transgenic mice . ^^^ The transgenic mice were healthy during their life spans , suggesting that AML 1 ETO alone is not sufficient for leukemogenesis . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
ETO , a target of t ( 8 ; 21 ) in acute leukemia , makes distinct contacts with multiple histone deacetylases and binds mSin3A through its oligomerization domain . t ( 8 ; 21 ) and t ( 16 ; 21 ) create two fusion proteins , AML 1 ETO and AML 1 MTG 16 , respectively , which fuse the AML 1 DNA binding domain to putative transcriptional corepressors , ETO and MTG 16 . ^^^ In addition , we show that expression of AML 1 ETO causes disruption of the cell cycle in the G ( 1 ) phase . ^^^ Disruption of the cell cycle required the ability of AML 1 ETO to repress transcription because a mutant of AML 1 ETO , Delta 469 , which removes the majority of the corepressor binding sites , had no phenotype . ^^^ Moreover , treatment of AML 1 ETO expressing cells with trichostatin A , an HDAC inhibitor , restored cell cycle control . ^^^ Thus , AML 1 ETO makes distinct contacts with multiple HDACs and an HDAC inhibitor biologically inactivates this fusion protein . . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The t ( 8 ; 21 ) is the second most frequent translocation in acute myeloid leukemia and creates a fusion between the DNA binding domain of AML 1 and the ETO ( also known as MTG 8 ) corepressor . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The patient tested positive by fluorescence in situ hybridization ( FISH ) for AML 1 splitting and positive by reverse transcriptase polymerase chain reaction ( RT PCR ) for chimeric AML1 / MTG8 messenger RNA ( mRNA ) , which indicated splitting of the MTG 8 gene on chromosome 8 ( q 22 ) and the AMLI gene on chromosome 22 ( q 22 ) . ^^^ After the disappearance of leukemic cells , FISH for AML 1 splitting was negative , and real time PCR results for quantitative chimeric AML1 / MTG 8 mRNA were less than the detectable level , however , RT PCR results for AML1 / MTG8 mRNA remained positive . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
Molecular characterization of genomic AML 1 ETO fusions in childhood leukemia . ^^^ T ( 8 ; 21 ) AML 1 ( CBFA 2 ) ETO ( MTG 8 ) is the most common chromosomal translocation in acute myeloid leukemia ( AML ) in both children and adults . ^^^ We sought to understand the structure and gain insight into the fusion process between AML 1 and ETO by sequencing genomic fusions in 17 primary childhood AMLs and two cell lines with t ( 8 ; 21 ) . ^^^ Testing for multimodality via smoothed bootstrap statistical methods suggested , however , the presence of two separate cluster regions within both the AML 1 and ETO breakpoint cluster regions . ^^^ All patients with available RNA expressed an AML 1 ETO mRNA fusion between exon 5 of AML 1 and exon 2 of ETO . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The AML 1 ETO fusion protein promotes the expansion of human hematopoietic stem cells . ^^^ The acute myelogenous leukemia 1 ( AML 1 ) ETO fusion protein is generated by the t ( 8 ; 21 ) , which is found in 40 % of AMLs of the French American British M 2 subtype . ^^^ AML 1 ETO interferes with the function of the AML 1 ( RUNX 1 , CBFA 2 ) transcription factor in a dominant negative fashion and represses transcription by binding its consensus DNA binding site and via protein protein interactions with other transcription factors . ^^^ Murine experiments suggest that AML 1 ETO expression may not be sufficient for leukemogenesis ; however , like the BCR ABL isoforms , the cellular background in which these fusion proteins are expressed may be critical to the phenotype observed . ^^^ Retroviral gene transfer was used to examine the effect of AML 1 ETO on the in vitro behavior of human hematopoietic stem and progenitor cells . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
Although DNA breakpoints in AML 1 and ETO ( at 8q22 ) cluster in a few introns , the mechanisms of DNA recombination resulting in t ( 8 ; 21 ) are unknown . ^^^ The correlation of specific chromatin structural elements , i . e . , topoisomerase 2 ( topo 2 ) DNA cleavage sites , DNase 1 hypersensitive sites , and scaffold associated regions , which have been implicated in chromosome recombination with genomic DNA breakpoints in AML 1 and ETO in t ( 8 ; 21 ) is unknown . ^^^ The breakpoints in AML 1 and ETO were clustered in the Kasumi 1 cell line and in 31 leukemia patients with t ( 8 ; 21 ) ; all except one had de novo AML . ^^^ Ten in vivo topo 2 DNA cleavage sites were mapped in AML 1 , including three in intron 5 and seven in intron 7a , and two were in intron 1b of ETO . ^^^ These sites correlated with genomic DNA breakpoints in both AML 1 and ETO , thus implicating them in the de novo 8 ; 21 translocation . . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
A high percentage of cases of acute myelogenous leukemia ( AML ) of the M 2 subtype show a rearrangement between the AML 1 and ETO genes . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The t ( 8 ; 21 ) fusion protein , AML 1 ETO , specifically represses the transcription of the p 14 ( ARF ) tumor suppressor in acute myeloid leukemia . ^^^ This translocation creates a fusion protein consisting of the acute myeloid leukemia 1 transcription factor and the eight twenty one corepressor ( AML 1 ETO ) , which represses transcription through AML 1 ( RUNX 1 ) DNA binding sites and immortalizes hematopoietic progenitor cells . ^^^ We have identified the p 14 ( ARF ) tumor suppressor , a mediator of the p 53 oncogene checkpoint , as a direct transcriptional target of AML 1 ETO . ^^^ AML 1 ETO repressed the p 14 ( ARF ) promoter and reduced endogenous levels of p 14 ( ARF ) expression in multiple cell types . ^^^ Chromatin immunoprecipitation assays demonstrated that AML 1 ETO was specifically bound to the p 14 ( ARF ) promoter . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
Hematopoietic stem cell expansion and distinct myeloid developmental abnormalities in a murine model of the AML 1 ETO translocation . ^^^ The t ( 8 ; 21 ) ( q 22 ; q 22 ) translocation , which fuses the ETO gene on human chromosome 8 with the AML 1 gene on chromosome 21 ( AML 1 ETO ) , is one of the most frequent cytogenetic abnormalities associated with acute myelogenous leukemia ( AML ) . ^^^ We have generated a murine model of the t ( 8 ; 21 ) translocation by retroviral expression of AML 1 ETO in purified hematopoietic stem cells ( HSC ) . ^^^ Animals reconstituted with AML 1 ETO expressing cells recapitulate the hematopoietic developmental abnormalities seen in the bone marrow of human patients with the t ( 8 ; 21 ) translocation . ^^^ HSC numbers in the bone marrow of 10 month posttransplant animals were 29 fold greater than in transplant matched control mice , suggesting that AML 1 ETO expression overrides the normal genetic control of HSC pool size . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
We have analyzed a series of 65 patients with t ( 8 ; 21 ) using several probes specific for the ETO and AML 1 regions . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
It originates from a gene rearrangement t ( 8 ; 21 ) that fuses the N terminal part of the key hematopoietic regulatory factor AML 1 ( RUNX 1 ) to the ETO ( MTG 8 ) repressor protein . ^^^ AML1ETO lacks the intranuclear targeting signal of the wild type AML 1 and is directed by the ETO component to alternate nuclear matrix associated sites . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The translocation t ( 8 ; 21 ) ( q 22 ; q 22 ) , which results in the fusion of the AML 1 ( RUNX 1 ) and ETO ( CBFA2T1 ) genes , is a recurrent aberration in acute myeloid leukemia ( AML ) , preferentially correlated with FAB M 2 , and has the highest incidence in childhood AML . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
Cloning and characterization of the 8 ; 21 chromosomal breakpoint identified AML 1 on chromosome 21 and ETO ( MTG 8 ) on chromosome 8 , and the resultant chimeric gene product , AML 1 / ETO . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The translocation fuses the DNA binding domain of AML 1 to nearly all of the ETO co repressor . ^^^ We found that AML 1 ETO repressed the promoter of p 14 ( ARF ) tumor suppressor in transient transfection assays and reduced endogenous levels of p 14 ( ARF ) expression in multiple cell types . ^^^ Chromatin immunoprecipitation assays demonstrated that AML 1 ETO bound to the p 14 ( ARF ) promoter . ^^^ Therefore , p 14 ( ARF ) is a direct transcriptional target of AML 1 ETO . . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
A cytogenetic study with a G banding method initially reported the karyotype as 45 , 10 , Y ; however , dual color , dual fusion fluorescence in situ hybridization ( FISH ) with probes for the AML 1 and the ETO genes showed an unusual pattern of signals , presenting one fusion signal on chromosome 21 . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The blast cells at the time of recurrence expressed the AML1 / ETO fusion transcript , and the breakpoint of the AML 1 gene was located on intron 5 . ^^^ Furthermore , the junction sequences between the AML 1 and the ETO genes , analyzed by long distance inverse polymerase chain reaction , proved to be completely identical . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The translocation was found to be involved in the AML 1 gene on the chromosome 21 and the ETO gene on the chromosome 8 , and resulted in the formation of AML1 / ETO fusion gene on the derivative chromosome 8 . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
METHODS : The rearrangements of AML 1 and ETO genes were detected by Southern Blot and the AML 1 ETO fusion gene by nested RT PCR combined with sequencing in K 562 cells treated with etoposide ( Vp 16 ) and doxorubicin ( DOX ) . ^^^ RESULTS : The rearrangements of AML 1 gene were detectable after DOX treatment at concentrations of 10 , 50 and 100 micro mol / L for 16 h , AML 1 ETO fusion gene appeared after 50 micro mol / L DOX treatment for 48 h . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The ( 8 ; 21 ) translocation between the AML 1 and ETO genes is seen in approximately 12 15 % of all acute myeloid leukemia ( AML ) and is a frequently observed nonrandom genetic alteration associated with AML . ^^^ Repression of AML 1 responsive hematopoietic genes by AML 1 ETO and the N CoR complex may play a mechanistic role in t ( 8 ; 21 ) leukemogenesis . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The 8 ; 21 translocation produces a fusion between the ETO gene and that encoding the myeloid transcription factor AML 1 . ^^^ The AML 1 ETO fusion substitutes the majority of the ETO protein for the coregulator recruitment domains of AML 1 . ^^^ Importantly , the proteins interacting with ETO are different from those of wild type AML 1 , suggesting that altered coregulator recruitment underlies the oncogenic properties of AML 1 ETO . ^^^ These investigations have provided mechanistic insight into corepressor recruitment by ETO and clues to the leukemogenic activity of AML 1 ETO . . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
AML 1 ETO decreases ETO 2 ( MTG 16 ) interactions with nuclear receptor corepressor , an effect that impairs granulocyte differentiation . ^^^ The t ( 8 ; 21 ) chromosome abnormality in acute myeloid leukemia targets the AML 1 and ETO genes to produce the leukemia fusion protein AML 1 ETO . ^^^ AML 1 ETO prevents granulocyte but not macrophage differentiation of murine 32Dcl3 granulocyte / macrophage progenitors . ^^^ We wished to examine another mechanism by which AML 1 ETO might impair granulocyte differentiation . ^^^ We demonstrate that AML 1 ETO decreases interactions between ETO 2 and N CoR . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The rearrangement results in fusion of the RUNX 1 ( also known as AML 1 ) and CBFA2T1 ( also known as ETO ) genes , generating a 5 ' RUNX1 / 3 ' CBFA2T1 transcriptionally active fusion gene on derivative chromosome 8 , but some cases with ins ( 21 ; 8 ) and ins ( 8 ; 21 ) have been observed . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
Cloning , expression , purification and crystallization of NHR 3 domain from acute myelogenous leukemia related protein AML 1 ETO . ^^^ This translocation creates a fusion between the acute myelogenous leukemia 1 ( AML 1 , a transcription factor ) gene on chromosome 21 and the eight twenty one ( ETO , a zinc finger nuclear protein ) gene on chromosome 8 , leading to the repression of certain AML 1 target genes . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
Breakpoint cluster regions of the AML 1 and ETO genes contain MAR elements and are preferentially associated with the nuclear matrix in proliferating HEL cells . ^^^ The spatial organization in interphase nuclei of the breakpoint cluster regions ( BCRs ) of the AML 1 and ETO genes frequently participating in reciprocal t ( 8 ; 21 ) translocations was studied using cytological and biochemical approaches . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The chromosomal translocation t ( 8 ; 21 ) fuses the AML 1 ( RUNX 1 ) gene on chromosome 21 and the ETO gene on chromosome 8 in human acute myeloid leukemias ( AMLs ) , resulting in expression of the chimeric transcription factor AML1 / ETO . ^^^ None of these genes has previously been described as a target of AML 1 , ETO or AML1 / ETO . ^^^
Interacting proteins: Q01196 and Q06455	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: Q01196 and Q06455	Pubmed	SVM Score :0.0
To analyze the function of AML 1 MTG8 in leukemic cells and to explore the possibility of AML 1 MTG8 targeted therapy , we designed nine small interfering RNAs ( siRNAs ) targeting a 25 nucleotide region spanning the fusion point of AML 1 and MTG 8 . ^^^ Both siRNAs did not reduce AML1b expression , but AM 2 siRNA showed slightly reducing activity against MTG8b mRNA that is 86 % homologous to the corresponded region of AML 1 MTG8 mRNA . ^^^ The siRNAs reduced neither the wild type AML 1 in Kasumi 1 cells nor wild type MTG8b in human erythroblastic leukemia ( HEL ) cells . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
Using a dual color fluorescence in situ hybridization ( FISH ) analysis with ETO and AML 1 probes , we demonstrated an ETO / AML1 fusion signal on the derivative chromosome 8 . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
Deletion of an AML 1 ETO C terminal NcoR / SMRT interacting region strongly induces leukemia development . ^^^ AML 1 ETO , which is a fusion protein generated by the 8 ; 21 translocation that is commonly associated with the development of acute myeloid leukemia , fuses the AML 1 runx family DNA binding transcription factor to the ETO corepressor that associates with histone deacetylase complexes . ^^^ Analyses have demonstrated that AML 1 ETO blocks AML 1 function and requires additional mutagenic events to promote leukemia . ^^^ Here , we report that the loss of the molecular events of AML 1 ETO C terminal NCoR / SMRT interacting domain transforms AML 1 ETO into a potent leukemogenic protein . ^^^ Contrary to full length AML 1 ETO , the truncated form promotes in vitro growth and does not obstruct the cell cycle machinery . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
Two genes , AML 1 and ETO , are fused together at the translocation breakpoint , resulting in the expression of a chimeric protein called AML 1 ETO . ^^^ AML 1 ETO is thought to interfere with normal AML 1 function , although the mechanism by which it does so is unclear . ^^^ Here , we have used Drosophila genetics to investigate two models of AML 1 ETO function . ^^^ In the first model , AML 1 ETO is a constitutive transcriptional repressor of AML 1 target genes , regardless of whether they are normally activated or repressed by AML 1 . ^^^ In the second model , AML 1 ETO dominantly interferes with AML 1 activity by , for example , competing for a common co factor . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The ( 8 ; 21 ) chromosomal translocation , which replaces the C terminus of AML 1 with the ETO protein , modifies subnuclear targeting of AML 1 in acute myeloid leukemia ( AML ) and results in defective myelopoiesis . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
Acute myeloid leukemia 1 ( AML 1 ) gene on chromosome 21 is involved in several chromosomal translocations , including t ( 8 ; 21 ) and t ( 16 ; 21 ) , that produce chimeric fusion proteins AML 1 eight twenty one ( ETO ) and AML myeloid transforming gene chromosome 16 ( MTG 16 ) , which contribute to leukemogenesis . ^^^ Using gel shift assay , we showed that AML 1 ETO and AML 1 MTG16 bound to a series of AML 1 consensus DNA binding sites with different affinities . ^^^ Using fluorescence recovery after photobleaching ( FRAP ) , we demonstrated that a fusion of AML 1 with ETO or MTG 16 exhibits reduced intranuclear mobility compared with wild type AML 1 or either fusion partner . ^^^ The dimerization domain ( nervy homology region 2 ) of ETO is responsible for the reduced mobility of AML 1 ETO . ^^^ Dual FRAP studies revealed that CBFbeta colocalized with AML 1 ETO within the nucleus , resulting in reduced mobility of CBFbeta . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
Leukemogenic AML 1 ETO fusion protein upregulates expression of connexin 43 : the role in AML 1 ETO induced growth arrest in leukemic cells . ^^^ AML 1 ETO , a fusion protein generated by the chromosomal translocation t ( 8 ; 21 ) , is frequently associated with acute myeloid leukemia ( AML ) . ^^^ In addition to blocking differentiation , AML 1 ETO is also shown to induce growth arrest in AML cells , which is unfavorable for leukemogenesis harboring the t ( 8 ; 21 ) translocation . ^^^ Here we provide the first demonstration that the conditional expression of AML 1 ETO by the ecdysone inducible system dramatically increases the expression of connexin 43 ( CX 43 ) , together with growth arrest at G 1 phase in leukemic U 937 cells . ^^^ We also show that the CX 43 induction inhibits the proliferation of U 937 cells at G 1 phase , while the suppression of CX 43 expression by small interfering RNA ( siRNA ) effectively overcomes the growth inhibitory effect of AML 1 ETO in leukemic cells . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The acute myeloid leukemia fusion protein AML 1 ETO targets E proteins via a paired amphipathic helix like TBP associated factor homology domain . ^^^ Up to 15 % of acute myeloid leukemias ( AMLs ) are characterized by the abnormal expression of the eight twenty one ( ETO ) transcriptional corepressor within an AML 1 ETO fusion protein . ^^^ The t ( 8 ; 21 ) chromosomal translocation serves not only to disrupt WT AML 1 function but also to introduce ETO activity during hematopoiesis . ^^^ AML 1 ETO was recently shown to inhibit E protein transactivation by physically displacing WT coactivator proteins in an interaction mediated by ETO . ^^^ Here , we present the 3D solution structure of the human ETO TAFH ( eTAFH ) domain implicated in AML 1 ETO : E protein interactions and report an unexpected fold similarity to paired amphipathic helix domains from the transcriptional corepressor Sin 3 . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The most commonly known AML 1 ETO fusion protein ( full length AML 1 ETO ) from this translocation has 752 amino acids and contains the N terminal portion of RUNX 1 ( also known as AML 1 , CBFalpha 2 or PEBP2alphaB ) , including its DNA binding domain , and almost the entire RUNX1T1 ( also known as MTG 8 or ETO ) protein . ^^^ Although alterations of gene expression and hematopoietic cell proliferation have been reported in the presence of AML 1 ETO , its expression does not lead to the development of leukemia . ^^^ Here , we report the identification of a previously unknown alternatively spliced isoform of the AML 1 ETO transcript , AML 1 ETO9a , that includes an extra exon , exon 9a , of the ETO gene . ^^^ AML 1 ETO9a encodes a C terminally truncated AML 1 ETO protein of 575 amino acids . ^^^ More importantly , coexpression of AML 1 ETO and AML 1 ETO9a results in the substantially earlier onset of AML and blocks myeloid cell differentiation at a more immature stage . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The MTG 8 ( ETO ) locus is involved in a reciprocal exchange with runx 1 in the t ( 8 ; 21 ) of acute myeloid leukemia . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The translocation creates a fusion protein that consists of the DNA binding domain of the RUNX 1 transcription factor fused to the MTG 8 transcriptional co repressor to create a potent transcriptional repressor . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The translocation creates a fusion protein that consists of the DNA binding domain of the RUNX 1 transcription factor fused to the MTG 8 transcriptional co repressor to create a potent transcriptional repressor . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
When fused to RUNX 1 , ETO is thought to mediate the formation of a repressive complex at RUNX 1 dependent genes . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
These effects are phenocopied by a chimeric protein containing ETO , the eight twenty one transcriptional repressor , fused to the Runx 1 DNA binding domain , which suggests the involvement of transcription repression mechanisms . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
While only three fusion partners of RUNX 1 namely ETO , ETV 6 and MTG 16 have been described so far , there is a plethora of ETV 6 fusion partners with about 20 partners described so far . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
The chromosomal translocation t ( 8 ; 21 ) , generating the AML 1 ETO fusion protein , is frequently associated with French American British ( FAB ) type M 2 acute myeloid leukemia ( AML ) . t ( 8 ; 21 ) fuses the runt domain from the hematopoietic transcription factor RUNX 1 with almost the entire transcriptional repressor ETO . ^^^
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
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Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
NA
Interacting proteins: Q01196 and Q06455	Pubmed	SVM Score :0.0
NA