DNMT3A and acute myeloid leukemia: The first confidently identified driver mutation was a homozygous nonsynonymous mutation in DNMT3A. DNMT3A is a DNA methyltransferase essential for development, especially for de novo DNA methylation in stem cells.16DNMT3A is mutated in numerous tumor types, but is mutated especially frequently in AML.20, 21 DNMT3A and its binding partner, DNMT3L form a tetramer: DNMT3L:DNMT3A:DNMT3A:DNMT3L.23 The most common DNMT3A mutations in AML occur at p.R882.