Within our tested time window, transient in vivo OSKM induction activates apoptosis in MLL-AF9 acute myeloid leukemia (AML) cells when grown in their natural habitat, either in vivo or in in vitro hematopoietic medium culture, but not in normal hematopoietic stem/progenitor cells. Here, KMT2A is linked to acute myeloid leukemia.