Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by hematopoietic stem-cell-derived clonal proliferation, leading to bone marrow (BM) fibrosis. Hematopoiesis alterations are closely associated with modifications of the BM microenvironment, characterized by defective interactions between vascular and endosteal niches. As such, neoangiogenesis, megakaryocytes hyperplasia and extensive bone marrow fibrosis, followed by osteosclerosis and bone damage, are the most relevant consequences of PMF. Moreover, bone tissue deposition, together with progressive fibrosis, represents crucial mechanisms of disabilities in patients. Although the underlying mechanisms of bone damage observed in PMF are still unclear, the involvement of cytokines, growth factors and bone marrow microenvironment resident cells have been linked to disease progression. Herein, we focused on the role of megakaryocytes and their alterations, associated with cytokines and chemokines release, in modulating functions of most of the bone marrow cell populations and in creating a complex network where impaired signaling strongly contributes to progression and disabilities.

中文翻译：

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专注于原发性骨髓纤维化的骨硬化进展

原发性骨髓纤维化（PMF）是一种骨髓增生性肿瘤，其特征是造血干细胞衍生的克隆增生，导致骨髓（BM）纤维化。造血功能改变与BM微环境的改变密切相关，其特征在于血管壁和骨膜内壁之间的相互作用不良。因此，新血管生成，巨核细胞增生和广泛的骨髓纤维化，然后是骨硬化和骨损伤，是PMF最相关的后果。此外，骨组织沉积以及进行性纤维化代表了患者残疾的关键机制。尽管在PMF中观察到的骨损伤的潜在机制仍不清楚，但是细胞因子的参与，生长因子和骨髓微环境驻留细胞已与疾病进展相关。在本文中，我们集中于巨核细胞及其与细胞因子和趋化因子释放相关的改变的作用，在调节大多数骨髓细胞群的功能以及创建复杂的网络（其中受损的信号传导强烈促进进展和残疾）方面。