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ASH 2020 | DNMT3AR882 mutations perturb hematopoietic progenitors via selective hypomethylation
Anna Nam, MD, Weill Cornell Medicine, New York, NY, discusses the findings of multi-omic single-cell sequencing studies in leukemia driver mutations in clonal hematopoiesis (CH). CH samples were obtained from multiple myeloma patients in remission and tested for DNMT3A mutations, with the DNMT3AR882 mutation variant being most commonly found. It was found that the DNMT3A mutation causes differentiation skews at key junctures of the hematopoiesis process, for example, a myeloid or lymphoid bias. Different technologies were used to establish the mutation status, transcription state, and the methylation status of the individual cells in the patient samples. Specific regions most affected by the DNMT3A mutation were identified. Overall, these findings suggest that DNMT3A can impact clonal hematopoiesis through hypermethylation and subsequent differentiation deregulation. This interview took place during the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, 2020.
