Recurrent missense, nonsense, and frameshift mutations have been identified in DNMT3A, a methyltransferase enzyme that catalyzes the transfer of methyl groups to cytosines in CpG islands of DNA (98) DNMT3A is recurrently mutated in de novo AML and at low frequency in MDS with dominance at older age. Here, DNMT3A is linked to acute myeloid leukemia.