Myelofibrosis is an enigmatic myeloproliferative neoplasm, despite noteworthy strides in understanding its genetic underpinnings. Driver mutations involving JAK2, CALR or MPL in 90% of patients mediate constitutive JAK‐STAT signaling which, in concert with epigenetic alterations (ASXL1, DNMT3A, SRSF2, EZH2, IDH1/2 mutations), play a fundamental role in disease pathogenesis. Aberrant immature megakaryocytes are a quintessential feature, exhibiting reduced GATA1 protein expression and secreting a plethora of pro‐inflammatory cytokines (IL‐1 ß, TGF‐ß), growth factors (b‐FGF, PDGF, VEGF) in addition to extra cellular matrix components (fibronectin, laminin, collagens). The ensuing disrupted interactions amongst the megakaryocytes, osteoblasts, endothelium, stromal cells and myofibroblasts within the bone marrow culminate in the development of fibrosis and osteosclerosis. Presently, prognostic assessment tools for primary myelofibrosis (PMF) are centered on genetics, with incorporation of cytogenetic and molecular information into the mutation‐enhanced (MIPSS 70‐plus version 2.0) and genetically‐inspired (GIPSS) prognostic scoring systems. Both models illustrate substantial clinical heterogeneity in PMF and serve as the crux for risk‐adapted therapeutic decisions. A major challenge remains the dearth of disease‐modifying drugs, whereas allogeneic transplant offers the chance of long‐term remission for some patients. Our review serves to synopsise current appreciation of the pathogenesis of myelofibrosis together with emerging management strategies.

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骨髓纤维化生物学与当代管理

骨髓纤维化是一种神秘的骨髓增生性肿瘤，尽管在了解其遗传基础方面取得了显着进步。90％的患者中涉及JAK2，CALR或MPL的驱动程序突变介导本构性JAK-STAT信号传导，与表观遗传学改变（ASXL1，DNMT3A，SRSF2，EZH2，IDH1 / 2突变），在疾病发病机理中起着根本作用。异常的未成熟巨核细胞是一个典型特征，表现出降低的GATA1蛋白表达并分泌过多的促炎细胞因子（IL-1ß，TGF-ß），生长因子（b-FGF，PDGF，VEGF），以及额外的细胞基质成分（纤连蛋白，层粘连蛋白，胶原蛋白）。骨髓中巨核细胞，成骨细胞，内皮，基质细胞和成肌纤维细胞之间随之而来的相互作用被破坏，最终导致纤维化和骨硬化的发展。目前，原发性骨髓纤维化（PMF）的预后评估工具以遗传学为中心，将细胞遗传学和分子信息纳入增强的突变中（MIPSS 70-plus 2.0版））和基因启发（GIPSS）的预后评分系统。两种模型均显示了PMF的大量临床异质性，并成为适应风险的治疗决策的症结所在。主要的挑战仍然是缺乏疾病改良药物，而同种异体移植为某些患者提供了长期缓解的机会。我们的审查有助于概述当前对骨髓纤维化发病机理的认识以及新兴的管理策略。