Accelerated senescence of bone marrow erythrocyte precursors in myelodysplastic syndrome

骨髓增生异常综合征中骨髓红细胞前体细胞加速衰老

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作者:Mengyuan Liu ,Liyan Yang ,Yumei Liu ,Haiyue Niu ,Mengying Zhang ,Zonghong Shao ,Limin Xing ,Huaquan Wang

Abstract

Background: Myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal hematopoietic disorders characterized by ineffective haematopoiesis, refractory cytopenia, and an increased risk of progression to acute myeloid leukaemia. This study investigates the presence of cellular senescence in bone marrow (BM) CD235a+ erythrocyte precursors of MDS patients and explores its correlation with anaemia. Methods: We assessed senescence-related markers and cell cycle distribution in BM CD235a+ erythrocyte precursors of MDS patients. Correlation analyses were conducted between the relative mRNA expression of p16INK4A, a key senescence regulator, and peripheral blood parameters. Results: MDS patients exhibited heightened cellular senescence characterized by increased SA-β-gal positivity, elevated p16INK4A and p21CIP1 expression, reduced CyclinD1 levels, and elevated IL-6. Cell cycle analysis revealed G0/G1 phase arrest. Correlation analysis established a negative association between p16INK4A expression and reticulocyte count, RBC count, haemoglobin concentration, indicating a direct link between BM erythrocyte precursors senescence and anaemia severity. Conclusion: MDS patients have accelerated senescence of bone marrow erythrocyte precursors, which is related to their anaemia. The observed correlation underscores the potential significance of senescence-targeted interventions in managing anaemia in MDS.Key MessagesBone marrow CD235a⁺ erythroid precursors in MDS patients exhibit accelerated senescence, characterized by cell cycle arrest and increased inflammatory markers. p16INK4A expression negatively correlates with anaemia severity, suggesting senescence as a key contributor to MDS-related anaemia.

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