We focus on the DNMT3AR882H missense mutation, which is the most frequent DNMT3A missense mutation in human AML,4,54 and is also the most frequently affected gene in clonal hematopoiesis.6,55,56 The effects of mutant DNMT3A have been intensely studied in the context of hematopoiesis, where mutant DNMT3A confers increased self-renewal in HSCs13,23 and a hyperinflammatory phenotype in mature myeloid cells.25 However, in leukemic cells, the role of DNMT3AR882H is less clear. The gene discussed is DNMT3A; the disease is acute myeloid leukemia.