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Haematologica ; 96(4): 617-20, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21134977

RESUMO

Impairment of CCAAT Enhancer Binding Protein alpha (CEBPA) function is a common finding in acute myeloid leukemia; nevertheless, its relevance for acute promyelocytic leukemia pathogenesis is unclear. We analyzed the expression and assessed the methylation status of the core and upstream promoters of CEBPA in acute promyelocytic leukemia at diagnosis. Patients with acute promyelocytic leukemia (n = 18) presented lower levels of CEBPA expression compared to healthy controls (n = 5), but higher levels than those in acute myeloid leukemia with t(8;21) (n = 9) and with inv(16) (n = 5). Regarding the core promoter, we detected no methylation in 39 acute promyelocytic leukemia samples or in 8 samples from controls. In contrast, analysis of the upstream promoter showed methylation in 37 of 39 samples, with 17 patients showing methylation levels over 30%. Our results corroborate data obtained in animal models showing that CEBPA is down-regulated in acute promyelocytic leukemia stem cells and suggest that epigenetic mechanisms may be involved.


Assuntos
Proteína alfa Estimuladora de Ligação a CCAAT/genética , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Metilação de DNA/genética , Regulação para Baixo , Regulação Leucêmica da Expressão Gênica , Leucemia Promielocítica Aguda , Regiões Promotoras Genéticas , Ilhas de CpG/genética , Epigenômica , Humanos , Leucemia Promielocítica Aguda/genética , Leucemia Promielocítica Aguda/fisiopatologia
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