The CEBPA gene is down-regulated in acute promyelocytic leukemia and its upstream promoter, but not the core promoter, is highly methylated

Autor(es)

Santana-Lemos, Barbara Amelia ^[1] ; Alencar de Lima Lange, Ana Paula ^[1] ; de Lira Benicio, Mariana Tereza ^[1] ; da Silva Jose, Thiago Donizete ^[1] ; Lucena-Araujo, Antonio Roberto ^[1] ; Krause, Alexandre ^[1] ; Thome, Carolina Hassibe ^[1] ; Rego, Eduardo Magalhaes ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Med Sch Ribeirao Preto, Natl Inst Sci & Technol Stem Cell & Cell Therapy, Dept Internal Med, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Med Sch Ribeirao Preto, Natl Inst Sci & Technol Stem Cell & Cell Therapy, Div Hematol Oncol, BR-14049900 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Haematologica; v. 96, n. 4, p. 617-620, APR 2011.
• Citações Web of Science: 10

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. (AU)

• Processo FAPESP: 01/08693-8 - Determinação do efeito da inativação do gene da proteína ligante do enhancer CCAAT (C/EBPa) na hematopoese de animais transgênicos PML-RARa
• Beneficiário: Eduardo Magalhães Rego
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 06/58136-1 - Estudo dos mecanismos epigeneticos reguladores da expressao do gene c/ebpalfa (ccaat enhancer binding protein alpha) na leucemia promielocitica aguda.
• Beneficiário: Barbara Amélia Aparecida Santana Lemos
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado