Ribosomal protein L5 induces cellular senescence via p53-p21-pRb pathway to mediate relapse of acute myeloid leukemia.

Cellular senescence plays a critical role in the relapse of acute myeloid leukemia (AML), yet the underlying mechanisms remain incompletely understood. Here, we investigated the function of ribosomal protein L5 (RPL5) in mediating cellular senescence and its impact on AML relapse. In relapsed AML patients, the proportion of senescent cells and the expression of RPL5 were elevated, compared to patients at newly diagnosised or in complete remission, suggesting a potential link between RPL5 and AML relapse. Following chemotherapy induction, a cellular senescence model was constructed using KG-1 A cells, with RPL5 expression significantly elevated. Knockdown of RPL5 suppressed cellular senescence and enhanced apoptosis, possibly due to different regulatory mechanisms for cell proliferation and senescence. Moreover, downregulation of RPL5 mitigated chemotherapy-induced senescence and improved the response of AML cells to chemotherapy drug. Mechanistically, RPL5 regulated cellular senescence via the p53-p21-pRb pathway and its downregulation led to a reduction in senescence-related protein expression levels. These findings suggest that RPL5 plays a critical role in mediating cellular senescence and chemotherapy response in AML, providing insights into novel therapeutic strategies for overcoming chemotherapy resistance and preventing disease relapse. Future studies may explore RPL5-targeted therapies and assess their clinical applicability in AML.