Taken together, our findings demonstrate a regulatory role of CD37 in MLL-AF9-induced AML, in which CD37 interacts with integrin family members (e.g., α4β7) and governs the survival of AML cells as well as the self-renewal of AML LSCs through integrin-mediated PI3K-AKT-BCL2/P27 signaling. Here, BCL2 is linked to acute myeloid leukemia.