DNMT3A mutants provide proliferating advantage with augmentation of self-renewal activity in the pathogenesis of AML in KMT2A-PTD-positive leukemic cells.

ABSTRACT: Acute myeloid leukemia (AML) with partial tandem duplication of histone-lysine N-methyltransferase 2A (KMT2A-PTD) is a subtype of AML and is associated with adverse survival, yet the molecular pathogenesis of KMT2A-PTD is not fully understood. DNA methyltransferase 3A (DNMT3A) is mutated in various myeloid neoplasms including AML, especially at the Arg882. Recently, it has been found that DNMT3A mutations frequently coexisted with KMT2A-PTD and are associated with inferior outcomes. We aimed to understand the biological role of DNMT3A mutation in KMT2A-PTD-positive cells. Herein, we found that overexpression of DNMT3A mutants (MT) in KMT2A-PTD-positive EOL-1 cells augmented cell proliferation and clonogenicity. Serial colony replating assays indicated that DNMT3A-MT increased the self-rene

SUBMITTER: Bera R 

PROVIDER: S-EPMC6997180 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature