DOT1L and acute myeloid leukemia: Balanced chromosome rearrangements between 11q23 and other chromosomes, present in ~5% of de novo AML, generate several distinct KMT2A fusion proteins,8 the most frequent of which are MLLT3 (not considered an adverse karyotype), MLLT1, MLLT10, ELL and MLLT4.9 In KMT2Ar-AML, the c-terminal portion of KMT2A – responsible for the methyl transferase activity of the enzyme – is replaced by a region of the fusion partner that leads to the recruitment, probably indirectly in most of the cases, of the DOT1L and TEFb complexes to the KMT2A fusion binding sites.