Characterization of the ETO and AML1-ETO proteins involved in 8;21 translocation in acute myelogenous leukemia.
The AML1 and ETO genes are disrupted by the nonrandom chromosomal translocation t(8;21) in acute myelogenous leukemia (AML). While the AML1 gene encodes a transcription factor indispensable for definitive hematopoiesis, the biological function of ETO is unknown. To understand the role of ETO and AML1-ETO in the pathogenesis of AML, the full length cDNAs of ETO and AML1-ETO were cloned and antibodies against AML1 and ETO proteins have been developed in our laboratory. Western blot analysis showed that ETO and AML1-ETO were identified as 70 kDa and 94 kDa proteins, respectively, and that both proteins, like AML1, were associated with the nuclear matrix. To examine whether the t(8;21)-positive AMLs expressed a 94-kDa AML1-ETO, protein fractions isolated from leukemia blasts of 10 patients with t(8;21)-positive AML and the Kasumi-1 cells were analyzed by Western blotting. The 94 kDa AML1-ETO fusion protein was detected in all samples. However, this fusion protein was not detectable in all 40 patients with t(8;21)-negative AMLs. The biological significance of AML1-ETO was examined in K562 cells, which stably overexpress AML1-ETO. We found that AML1-ETO blocked the erythroid differentiation of K562 cells induced by low doses of Ara-C. Thus, t(8;21)-positive AMLs appear to overexpress the AML1-ETO fusion protein, which may be responsible for differentiation block and leukemogenesis in AML.
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Division of Laboratory Medicine, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Claxton
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Kornblau
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Fan
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Mu
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Chang
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D016475:3T3 Cells; D000818:Animals; D000906:Antibodies / Q000097:blood; D002454:Cell Differentiation / Q000235:genetics; D002891:Chromosomes, Human, Pair 21; D002898:Chromosomes, Human, Pair 8; D003001:Cloning, Molecular; D050676:Core Binding Factor Alpha 2 Subunit; D018076:DNA, Complementary / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000276:immunology; D015672:Erythroid Precursor Cells / Q000473:pathology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics* / Q000276:immunology; D011518:Proto-Oncogene Proteins; D000075142:RUNX1 Translocation Partner 1 Protein; D014157:Transcription Factors / Q000235:genetics* / Q000276:immunology; D014178:Translocation, Genetic
D000906:Antibodies; D050676:Core Binding Factor Alpha 2 Subunit; D018076:DNA, Complementary; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D000075142:RUNX1 Translocation Partner 1 Protein; C493728:RUNX1 protein, human; C082222:RUNX1T1 protein, human; C493726:Runx1 protein, mouse; D014157:Transcription Factors