In line, we found strong anti-proliferative effects, induction of myeloid differentiation, and apoptosis upon mutagenesis of the SETD2 SET domain in the human MLL-rearranged AML cell lines MOLM-13 and MV4-11, THP-1, and NOMO-1 (Fig. 6c; Supplementary Fig. 9b-f, Supplementary Fig. 10). This evidence concerns the gene KMT2A and acute myeloid leukemia.