PLK1 inhibition impairs erythroid differentiation

• DOI: 10.3389/fcell.2024.1516704
• Publication Date: 2024-12-23T06:38:41Z
• Authors: Peijun Jia; Yan Li; Lulu Duan; Jingxin Zhang; Yuanlin Xu; Huan Zhang; Chenghui Wang; Yaqian Gong; Ying Zhang; Longzhen Zhao; Yumin Huang; Shijie Zhang
• Keywords: PLK1; Ineffective erythropoiesis

Polo-like kinase 1 (PLK1), a key regulator of the G2/M phase in mitosis, is frequently overexpressed numerous tumors. Although PLK1 inhibitors have emerged as promising therapeutic agents for cancer, their use has been linked to significant anemia subset patients, yet underlying mechanisms remain poorly understood. In this study, we utilized an vitro human umbilical cord blood-derived CD34 + cell-based erythroid differentiation system, alongside murine model, investigate impact on erythropoiesis. Our results indicate that inhibitors, specifically GSK461364 and BI6727, significantly suppress proliferation cells, resulting cell cycle arrest, increased apoptosis formation abnormally nucleated late-stage erythroblasts. vivo , administration mice induced severe anemia, evidenced by marked reduction red blood cells hemoglobin levels. More specifically, inhibition impaired commitment hematopoietic stem bone marrow, abnormal accumulation BFU-E reduced CFU-E, decrease number terminal erythrocytes. Mechanistically, primarily induce reducing Mitochondrial membrane potential arresting at phase. Overall, our findings underscore critical role erythropoiesis shed light inhibitor-induced providing essential guidance developing strategies prevent manage clinical applications PLK1-targeted therapies.