| Literature DB >> 27300438 |
Liubin Yang1,2, Benjamin Rodriguez3, Allison Mayle1,2, Hyun Jung Park3, Xueqiu Lin3,4, Min Luo2, Mira Jeong2, Choladda V Curry5, Sang-Bae Kim6, David Ruau7, Xiaotian Zhang1,2, Ting Zhou8, Michael Zhou9, Vivienne I Rebel8, Grant A Challen10, Berthold Gottgens7, Ju-Seog Lee6, Rachel Rau11, Wei Li3, Margaret A Goodell1,3,2,6.
Abstract
DNMT3A, the gene encoding the de novo DNA methyltransferase 3A, is among the most frequently mutated genes in hematologic malignancies. However, the mechanisms through which DNMT3A normally suppresses malignancy development are unknown. Here, we show that DNMT3A loss synergizes with the FLT3 internal tandem duplication in a dose-influenced fashion to generate rapid lethal lymphoid or myeloid leukemias similar to their human counterparts. Loss of DNMT3A leads to reduced DNA methylation, predominantly at hematopoietic enhancer regions in both mouse and human samples. Myeloid and lymphoid diseases arise from transformed murine hematopoietic stem cells. Broadly, our findings support a role for DNMT3A as a guardian of the epigenetic state at enhancer regions, critical for inhibition of leukemic transformation.Entities:
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Year: 2016 PMID： 27300438 PMCID： PMC4908977 DOI： 10.1016/j.ccell.2016.05.003
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743