Characterization of the ETO and AML1-ETO proteins involved in 8;21 translocation in acute myelogenous leukemia.
Eur J Haematol
; 60(4): 217-25, 1998 Apr.
Article
em En
| MEDLINE
| ID: mdl-9579874
ABSTRACT
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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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Translocação Genética
/
Leucemia Mieloide Aguda
/
Proteínas Proto-Oncogênicas
/
Proteínas de Ligação a DNA
/
Proteínas de Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
1998
Tipo de documento:
Article