Zhang Wanqiu, Liu Linlin, Chen Ruotong, Yan Haotian, Zhang Qing, Ren Xiyang, Wang Huiping, Dong Yi, Xue Wanying, Zhai Zhimin, Tao Qianshan
Department of Hematology, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, Anhui, P.R. China.
Hematological Laboratory, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, Anhui, P.R. China.
Sci Rep. 2025 Jul 29;15(1):27649. doi: 10.1038/s41598-025-12108-1.
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.
细胞衰老在急性髓系白血病（AML）复发中起关键作用，但其潜在机制仍未完全阐明。在此，我们研究了核糖体蛋白L5（RPL5）在介导细胞衰老中的功能及其对AML复发的影响。与新诊断或完全缓解的患者相比，复发AML患者中衰老细胞的比例和RPL5的表达升高，提示RPL5与AML复发之间存在潜在联系。化疗诱导后，使用KG-1 A细胞构建细胞衰老模型，RPL5表达显著升高。敲低RPL5可抑制细胞衰老并增强凋亡，这可能是由于细胞增殖和衰老的调控机制不同所致。此外，RPL5的下调减轻了化疗诱导的衰老并改善了AML细胞对化疗药物的反应。机制上，RPL5通过p53-p21-pRb途径调节细胞衰老，其下调导致衰老相关蛋白表达水平降低。这些发现表明，RPL5在介导AML细胞衰老和化疗反应中起关键作用，为克服化疗耐药性和预防疾病复发的新治疗策略提供了见解。未来的研究可能探索靶向RPL5的疗法并评估其在AML中的临床适用性。
