CpG Island Hypermethylation Mediated by DNMT3A Is a Consequence of AML Progression.

ABSTRACT: DNMT3A mutations occur in ∼25% of acute myeloid leukemia (AML) patients. The most common mutation, DNMT3A^R882H, has dominant negative activity that reduces DNA methylation activity by ∼80% in vitro. To understand the contribution of DNMT3A-dependent methylation to leukemogenesis, we performed whole-genome bisulfite sequencing of primary leukemic and non-leukemic cells in patients with or without DNMT3A^R882 mutations. Non-leukemic hematopoietic cells with DNMT3A^R882H displayed focal methylation loss, suggesting that hypomethylation antedates AML. Although virtually all AMLs with wild-type DNMT3A displayed CpG island hypermethylation, this change was not associated with gene silencing and was essentially absent in AMLs with DNMT3A^R882 mutations. Pr

SUBMITTER: Spencer DH 

PROVIDER: S-EPMC5328582 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature