Aberrant histone modifications contribute to the derepression of self-renewal genes such as HOXA/B and MEIS1 in committed hematopoietic progenitors, which is considered a key mechanism of leukemogenesis in MLL-rearranged (MLL-r) and NPM1-mutated AML. The gene discussed is KMT2A; the disease is acute myeloid leukemia.