Spampinato Mariarita, Giallongo Cesarina, Romano Alessandra, Longhitano Lucia, La Spina Enrico, Avola Roberto, Scandura Grazia, Dulcamare Ilaria, Bramanti Vincenzo, Di Rosa Michelino, Vicario Nunzio, Parenti Rosalba, Li Volti Giovanni, Tibullo Daniele, Palumbo Giuseppe A
Section of Biochemistry, Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy.
Department of Medical and Surgical Sciences and Advanced Technologies "G.F. Ingrassia", University of Catania, 95123 Catania, Italy.
Biomolecules. 2021 Jan 19;11(1):122. doi: 10.3390/biom11010122.
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.
原发性骨髓纤维化（PMF）是一种骨髓增殖性肿瘤，其特征为造血干细胞来源的克隆性增殖，导致骨髓（BM）纤维化。造血改变与BM微环境的改变密切相关，其特征是血管龛和骨内膜龛之间的相互作用存在缺陷。因此，新生血管形成、巨核细胞增生和广泛的骨髓纤维化，随后出现骨硬化和骨损伤，是PMF最相关的后果。此外，骨组织沉积以及进行性纤维化是患者致残的关键机制。虽然PMF中观察到的骨损伤潜在机制仍不清楚，但细胞因子、生长因子和骨髓微环境驻留细胞的参与与疾病进展有关。在此，我们重点关注巨核细胞的作用及其改变，这些改变与细胞因子和趋化因子的释放相关，在调节大多数骨髓细胞群体的功能以及创建一个复杂网络方面发挥作用，在这个网络中受损的信号传导强烈促进疾病进展和致残。
