Dysregulation of the menin-KMT2A and polycomb repressive (PRC1/2) complexes in MLL-rearranged and NPM1-mutated acute myeloid leukemia (AML) contributes to the aberrant expression of self-renewal genes in hematopoietic stem and progenitor cells. The gene discussed is KMT2A; the disease is acute myeloid leukemia.