The CEBPA gene is down-regulated in acute promyelocytic leukemia and its upstream promoter, but not the core promoter, is highly methylated.
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.
Hematology/Oncology Division, Department of Internal Medicine, Medical School of Ribeirão Preto, University of São Paulo, Av Bandeirantes 3900, CEP 14049-900, Ribeirão Preto, SP, Brazil. emrego@hcrp.fmrp.usp.br
Bárbara Amélia
BA
Santana-Lemos
Ana Paula Alencar
AP
de Lima Lange
Mariana Tereza
MT
de Lira Benício
Thiago Donizete da Silva
TD
José
Antônio Roberto
AR
Lucena-Araújo
Alexandre
A
Krause
Carolina Hassibe
CH
Thomé
Eduardo Magalhães
EM
Rego
D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics* / Q000378:metabolism*; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D015536:Down-Regulation; D057890:Epigenomics; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000503:physiopathology; D011401:Promoter Regions, Genetic
D022763:CCAAT-Enhancer-Binding Protein-alpha