DNMT3A and acute myeloid leukemia: We focused on DNMT3AR882 missense mutations, which are among the most frequently occurring founding mutations in human clonal hematopoiesis and acute myeloid leukemia (AML).4–6 Mutations in DNMT3A impair its ability to methylate DNA CpGs7–9, leading to increased self-renewal of hematopoietic stem cells (HSCs),10 and have been associated with poor treatment outcomes in AML.4,11 During disease evolution, DNMT3AR882 missense mutations are frequently acquired early, preceding leukemic transformation,12 suggesting a critical role in disease initiation.