The CEBPA gene is down-regulated in acute promyelocytic leukemia and its upstream promoter, but not the core promoter, is highly methylated
| Autor: | Antonio R. Lucena-Araujo, Eduardo Magalhães Rego, Carolina Hassibe Thomé, Barbara A. Santana-Lemos, Ana Paula Alencar de Lima Lange, Mariana Tereza Lira Benício, Thiago Donizete da Silva José, Alexandre Krause |
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| Rok vydání: | 2010 |
| Předmět: |
Acute promyelocytic leukemia
Epigenomics Down-Regulation Promyelocytic leukemia protein Leukemia Promyelocytic Acute hemic and lymphatic diseases CEBPA medicine CCAAT-Enhancer-Binding Protein-alpha Humans Promoter Regions Genetic biology Gene Expression Regulation Leukemic Brief Report Myeloid leukemia EXPRESSÃO GÊNICA Promoter Hematology Methylation DNA Methylation medicine.disease Molecular biology DNA methylation Cancer research biology.protein CpG Islands |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| ISSN: | 1592-8721 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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