A Model System for Studying the DNMT3A Hotspot Mutation (DNMT3AR882) Demonstrates a Causal Relationship between Its Dominant-Negative Effect and Leukemogenesis.
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ABSTRACT: Mutation of DNA methyltransferase 3A at arginine 882 (DNMT3AR882mut) is prevalent in hematologic cancers and disorders. Recently, DNMT3AR882mut has been shown to have hypomorphic, dominant-negative, and/or gain-of-function effects on DNA methylation under different biological contexts. However, the causal role for such a multifaceted effect of DNMT3AR882mut in leukemogenesis remains undetermined. Here, we report TF-1 leukemia cells as a robust system useful for modeling the DNMT3AR882mut-dependent transformation and for dissecting the cause-effect relationship between multifaceted activities of DNMT3AR882mut and leukemic transformation. Ectopic expression of DNMT3AR882mut and not wild-type DNMT3A promoted TF-1 cell transform
SUBMITTER: Lu R
PROVIDER: S-EPMC6897384 | biostudies-literature | 2019 Jul
REPOSITORIES: biostudies-literature
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