Department of Life Science and Public Health, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.
Int J Mol Sci. 2024 Aug 14;25(16):8860. doi: 10.3390/ijms25168860.
Philadelphia-Negative Myeloproliferative neoplasms (MPNs) are a diverse group of blood cancers leading to excessive production of mature blood cells. These chronic diseases, including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), can significantly impact patient quality of life and are still incurable in the vast majority of the cases. This review examines the mechanobiology within a bone marrow niche, emphasizing the role of mechanical cues and the primary cilium in the pathophysiology of MPNs. It discusses the influence of extracellular matrix components, cell-cell and cell-matrix interactions, and mechanosensitive structures on hematopoietic stem cell (HSC) behavior and disease progression. Additionally, the potential implications of the primary cilium as a chemo- and mechanosensory organelle in bone marrow cells are explored, highlighting its involvement in signaling pathways crucial for hematopoietic regulation. This review proposes future research directions to better understand the dysregulated bone marrow niche in MPNs and to identify novel therapeutic targets.
费城阴性骨髓增殖性肿瘤（MPN）是一组导致成熟血细胞过度产生的血液癌症。这些慢性疾病，包括真性红细胞增多症（PV）、特发性血小板增多症（ET）和原发性骨髓纤维化（PMF），会显著影响患者的生活质量，且在绝大多数情况下仍无法治愈。这篇综述检查了骨髓龛内的力学生物学，强调了机械线索和初级纤毛在 MPN 病理生理学中的作用。它讨论了细胞外基质成分、细胞-细胞和细胞-基质相互作用以及机械敏感结构对造血干细胞（HSC）行为和疾病进展的影响。此外，还探讨了初级纤毛作为骨髓细胞中的化学和机械感受器细胞器的潜在意义，强调了其在造血调节的关键信号通路中的参与。这篇综述提出了未来的研究方向，以更好地理解 MPN 中失调的骨髓龛，并确定新的治疗靶点。
