While acute inactivation of STAG2 in non-transformed human cells results in cell cycle arrest, STAG2 homozygous deletion or inactivating truncating mutations are commonly selected for during the development of glioblastoma, urothelial carcinoma, Ewing sarcoma, acute myeloid leukemia, and other human cancer types, whereby this genetic inactivation likely functions to promote some aspect of tumor survival or growth. Here, STAG2 is linked to acute myeloid leukemia.