In acute leukemias, KMT2A rearrangements aberrantly recruit transcriptional cofactors, activating oncogenic gene programs; in solid tumors, loss-of-function mutations in KMT2C/D disrupt enhancer-mediated regulatory networks, compromising cellular identity and genome stability; in neurodevelopmental disorders, germline haploinsufficiency of KMT2A/B/D impairs developmental epigenetic programming. This evidence concerns the gene KMT2C and acute leukemia.