Journal of Clinical Medicine Research

Objective: To analyze the mechanism of CD37 in regulating the PI3K/AKT signaling pathway in acute myeloid leukemia (AML). Methods: AML mouse models were established with CD37 knockout (CD37⁻/⁻ group) and wild-type (CD37fl/fl group). The function of leukemia stem cells (LSCs) was evaluated by flow cytometry, colony formation assay, and serial transplantation assay. Signaling pathway changes were analyzed by RNA-seq and Western blot. The interaction between CD37 and integrin was verified by co-immunoprecipitation. Results: Compared with the CD37fl/fl group, the CD37⁻/⁻ group showed decreased GFP⁺ cells in peripheral blood, reduced bone marrow blasts, and prolonged median survival (P<0.05). RNA-seq revealed that the PI3K/AKT pathway was the most significantly enriched pathway. The levels of p-FAK and p-PI3K were decreased in the CD37⁻/⁻ group. Co-immunoprecipitation demonstrated that CD37 directly bound to integrin α4 and β7 subunits, and the expression of integrin α4 and β7 was downregulated after CD37 deletion (P<0.05). Conclusion: CD37 regulates the self-renewal of LSCs by activating the PI3K/AKT pathway through integrin α4β7, and may serve as a potential safe target for AML therapy.