CD37 Regulates the Self-Renewal of Leukemic Stem Cells via Integrin Mediated Signaling in Acute Myeloid Leukemia

Leukemic stem cells (LSCs) are a small subset of leukemia cells which drive leukemia initiation and maintenance. Herein, we report that CD37, a member of transmembrane 4 superfamily (TM4SF), regulates the survival of acute myeloid leukemia (AML) cells as well as the self-renewal of AML LSCs. The downregulation of CD37 retarded proliferation and increased apoptosis in human AML cell lines THP-1 and OCI-AML2. Deficiency of CD37 in vivo had a minimal effect on normal hematopoiesis, but significantly impeded leukemia maintenance and propagation, which led to increased apoptosis and decreased cell cycle entry in AML blasts as well as impaired colony formation and declined frequency of AML LSCs in the serial transplantation. Furthermore, CD37 interacted with integrin a4ß7 and activated PI3K-AKT pathway mediated by integrin signaling. Our study provides novel insights for targeted therapy of AML, indicating CD37 as a safe and effective target for immunotherapy. Overall design: RNA-seq profiling of CD37 fl/fl and CD37 -/- bone marrow YFP+,c-kit+ LSCs obtained from the secondary transplantation of MLL-AF9 AML mice model at week 6. Each genotype has 2 independent replicates.