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Characterization of the ETO and AML1–ETO proteins involved in the 8;21 translocation in acute myelogenous leukemia
Author(s) -
Le XiaoFeng,
Claxton David,
Kornblau Steve,
Fan YouHong,
Mu ZhaoMei,
Chang KunSang
Publication year - 1998
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.1600-0609.1998.tb01027.x
Subject(s) - fusion protein , chromosomal translocation , leukemia , western blot , k562 cells , biology , microbiology and biotechnology , chronic myelogenous leukemia , haematopoiesis , blot , cancer research , gene , immunology , genetics , stem cell , recombinant dna
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.