In primary human BM cells expressing KMT2A-PTD and DNMT3A-MT showed hyperproliferation and self-renewal clonogenic potential compared to DNMT3A-WT with KMT2A-PTD, suggesting a critical role of mutant DNMT3A in AML patients with KMT2A-PTD. Here, DNMT3A is linked to acute myeloid leukemia.