原句结构不变： 原发性骨髓纤维化（PMF）是一种干细胞源性克隆性骨髓增生性肿瘤（MPN），通常伴随JAK2、CALR或MPL突变，但并非总是如此；其他特征包括骨髓网状纤维/胶原纤维增生、异常的炎性细胞因子表达、贫血、肝脾肿大、骨外造血、全身症状、消瘦、白血病进展风险和缩短寿命。骨髓检查与细胞遗传学和突变研究提供综合诊断信息；JAK2、CALR或MPL突变的存在是可预期的，但不是必需的。国际共识分类将“预纤维化”与“明显纤维化”PMF区分开来；前者可能在表现上类似于本质性血小板增多症（ET）。约15%的ET或红细胞增多症（PV）患者可能进展为后期ET/PV MF。SRSF2、ASXL1和U2AF1-Q157突变预示PMF患者预后不良；RAS/CBL突变预示对盐酸如昔利班治疗的抵抗力。CALR突变型1/类似突变与良好的预后有关。非常高风险的异常包括-7、inv （3）、i（17q）、+21、+19、12p-和11q-。有利的风险异常包括正常核型或孤立的+9、13q-、20q-、1q异常和Y染色体丢失。当代预后系统包括基于遗传学的预后评分系统（GIPSS）和MIPSS70+版本2.0（MIPSSv2；突变和核型增强国际预后评分系统）。GIPSS完全基于突变和核型；MIPSSv2还包括临床危险因素。对于MIPSSv2的“低”和“非常低”风险疾病（预计10年存活率为56%-92%），建议仅进行观察；同种异体造血干细胞移植（AHSCT）是“非常高”和“高”风险疾病的首选治疗选择（预计10年存活率为0-13%），并且对中等风险疾病的仔细选择患者（预计10年存活率约为30%）也适用。MF的药物治疗目前仅为姑息治疗，主要针对贫血、脾肿大和全身症状。JAK2抑制剂：盐酸如昔利班、费格拉替尼和帕克替尼获得FDA批准，并分别用于治疗氢氧化脲治疗失败、如昔利班治疗失败或血小板计数<50×10（9）/L的患者。Momelotinib是另一种JAK2抑制剂，预计在2023年获批并显示出促红细胞生成的益处，除了影响脾脏和症状反应。脾切除用于药物难治性脾肿大，局部放疗用于非肝脾EMH和肢体骨痛。目前正在进行临床试验的新药物，单独或与如昔利班联合使用，其初步结果在2022年ASH年会上进行了介绍并在本综述中得到了突出。©2023 Wiley Periodicals LLC.

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by stem cell-derived clonal myeloproliferation that is often but not always accompanied by JAK2, CALR, or MPL mutations; additional features include bone marrow reticulin/collagen fibrosis, aberrant inflammatory cytokine expression, anemia, hepatosplenomegaly, extramedullary hematopoiesis (EMH), constitutional symptoms, cachexia, risk of leukemic progression, and shortened survival.Bone marrow examination with cytogenetic and mutation studies provides integrated diagnostic information; presence of JAK2, CALR or MPL mutation is expected but not required.The International Consensus Classification distinguishes "prefibrotic" from "overtly fibrotic" PMF; the former might mimic essential thrombocythemia (ET) in its presentation. Approximately 15% of patients with ET or polycythemia vera (PV) might progress into post-ET/PV MF.SRSF2, ASXL1, and U2AF1-Q157 mutations predict inferior survival in PMF; RAS/CBL mutations predict resistance to ruxolitinib therapy. Type 1/like CALR mutation is associated with superior survival.Very high-risk abnormalities include -7, inv (3), i(17q), +21, +19, 12p- and 11q-. Favorable risk abnormalities include normal karyotype or isolated +9, 13q-, 20q-, 1q abnormalities and loss of Y chromosome.Contemporary prognostic systems include GIPSS (genetically-inspired prognostic scoring system) and MIPSS70+ version 2.0 (MIPSSv2; mutation-and karyotype-enhanced international prognostic scoring system). GIPSS is based exclusively on mutations and karyotype; MIPSSv2 includes, in addition, clinical risk factors.Observation alone is advised for MIPSSv2 "low" and "very low" risk disease (estimated 10-year survival 56%-92%); allogeneic hematopoietic stem cell transplant (AHSCT) is the preferred treatment of choice for "very high" and "high" risk disease (estimated 10-year survival 0-13%), as well as in carefully selected patients with intermediate-risk disease (estimated 10-year survival 30%). Drug therapy in MF is currently palliative and targets anemia, splenomegaly, and constitutional symptoms. JAK2 INHIBITORS: Ruxolitinib, fedratinib, and pacritinib are FDA approved and respectfully utilized in patients failing treatment with hydroxyurea, ruxolitinib, or with platelet count <50 × 10 (9)/L. Momelotinib is another JAK2 inhibitor that is poised for approval sometime in 2023 and has shown erythropoietic benefits, in addition to affecting spleen and symptom responses.Splenectomy is considered for drug-refractory splenomegaly and involved field radiotherapy for non-hepatosplenic EMH and extremity bone pain.New agents, alone or in combination with ruxolitinib, are currently under clinical trial investigation (ClinicalTrials.gov) and preliminary results were presented at the 2022 ASH annual meeting and highlighted in the current review.© 2023 Wiley Periodicals LLC.