Janus激酶2抑制剂（JAKi）现在已经成为治疗原发性和继发性骨髓纤维化（MF）的治疗工具之一。MF患者忍受着缩短的生存期和低劣的生活质量（QoL）。异基因干细胞移植目前是MF唯一的治疗方式，具有治愈疾病或延长生存期的潜力。相比之下，目前MF的药物治疗针对的是QoL，而不是改变疾病的自然历史。在骨髓增生性肿瘤（包括MF）中发现JAK2和其他JAK-STAT活化突变（即CALR和MPL），促进了几种JAKi的开发，这些JAKi不一定特异于致癌突变本身，而是证明在对抗JAK-STAT信号传导方面具有有效性，导致炎性细胞因子和骨髓增生受抑制。这种非特异性活动对宪法症状和脾肿大产生了临床有益的影响，并因此获得了三种小分子JAKi的FDA批准：鲁索利替尼，费德拉替尼和帕克替尼。第四种JAKi，莫莫利替尼，即将获得FDA批准，并已被证明在缓解MF的输血依赖性贫血方面提供了额外的益处。母亲利替尼对贫血的有益作用归因于ACVR1受体的抑制，最新信息表明帕克替尼也有类似的作用。ACRV1介导SMAD2/3信号传导，有助于hepcidin生产和铁限制性造血的上调。ACRV1的治疗靶向提高了与无效造血有关的其他髓系肿瘤的治疗前景，如具有环形侧红细胞或SF3B1突变的骨髓增生异常综合症（MDS），尤其是那些合并JAK2突变和血小板增多症的患者。

Janus kinase 2 inhibitors (JAKi) are now part of the therapeutic armamentarium for primary and secondary myelofibrosis (MF). Patients with MF endure shortened survival and poor quality of life (QoL). Allogeneic stem cell transplant is currently the only treatment modality in MF with the potential to cure the disease or prolong survival. By contrast, current drug therapy in MF targets QoL and does not modify the natural history of the disease. The discovery of JAK2 and other JAK-STAT activating mutations (i.e., CALR and MPL) in myeloproliferative neoplasms, including MF, has facilitated the development of several JAKi that are not necessarily specific to the oncogenic mutations themselves but proved effective in countering JAK-STAT signaling, resulting in suppression of inflammatory cytokines and myeloproliferation. This non-specific activity resulted in clinically favorable effects on constitutional symptoms and splenomegaly and, consequently, FDA approval of three small molecule JAKi: ruxolitinib, fedratinib, and pacritinib. A fourth JAKi, momelotinib, is poised for FDA approval soon and has been shown to provide additional benefit in alleviating transfusiondependent anemia in MF. The salutary effect of momelotinib on anemia has been attributed to inhibition of activin A receptor, type 1 (ACVR1) and recent information suggests similar effect from pacritinib. ACRV1 mediates SMAD2/3 signalling that contributes to upregulation of hepcidin production and iron-restricted erythropoiesis. Therapeutic targeting of ACRV1 raises therapeutic prospects in other myeloid neoplasms associated with ineffective erythropoiesis, such as myelodysplastic syndromes with ring sideroblasts or SF3B1 mutation, especially those with co-expression of JAK2 mutation and thrombocytosis.