Tufts University School of Medicine, Boston, MA, USA.
Incyte Corporation, Wilmington, DE, USA.
Int J Gen Med. 2014 Jan 29;7:89-101. doi: 10.2147/IJGM.S51800. eCollection 2014.
Myelofibrosis (MF) is a rare chronic BCR-ABL1 (breakpoint cluster region-Abelson murine leukemia viral oncogene homologue 1)-negative myeloproliferative neoplasm characterized by progressive bone marrow fibrosis, inefficient hematopoiesis, and shortened survival. The clinical manifestations of MF include splenomegaly, consequent to extramedullary hematopoiesis, cytopenias, and an array of potentially debilitating abdominal and constitutional symptoms. Dysregulated Janus kinase (JAK)-signal transducer and activator of transcription signaling underlies secondary disease-associated effects in MF, such as myeloproliferation, bone marrow fibrosis, constitutional symptoms, and cachexia. Common fatal complications of MF include transformation to acute leukemia, thrombohemorrhagic events, organ failure, and infections. Potential complications from hepatosplenomegaly include portal hypertension and variceal bleeding, whereas extramedullary hematopoiesis outside the spleen and liver - depending on the affected organ - may result in intracranial hypertension, spinal cord compression, pulmonary hypertension, pleural effusions, lymphadenopathy, skin lesions, and/or exacerbation of abdominal symptoms. Although allogeneic stem cell transplantation is the only potentially curative therapy, it is suitable for few patients. The JAK1/JAK2 inhibitor ruxolitinib is effective in improving splenomegaly, MF-related symptoms, and quality-of-life measures. Emerging evidence that ruxolitinib may be associated with a survival benefit in intermediate- or high-risk MF suggests the possibility of a disease-modifying effect. Consequently, ruxolitinib could provide a treatment backbone to which other (conventional and novel) therapies may be added for the prevention and effective management of specific MF-associated complications.
骨髓纤维化（MF）是一种罕见的慢性 BCR-ABL1（断裂点簇区-急性髓系白血病病毒致癌基因同源物 1）阴性骨髓增殖性肿瘤，其特征为进行性骨髓纤维化、无效造血和生存时间缩短。MF 的临床表现包括脾肿大，继发于骨髓外造血、细胞减少症以及一系列潜在使人虚弱的腹部和全身症状。失调的 Janus 激酶（JAK）-信号转导子和转录激活子信号通路是 MF 继发疾病相关效应的基础，如骨髓增殖、骨髓纤维化、全身症状和恶病质。MF 的常见致命并发症包括转化为急性白血病、血栓出血事件、器官衰竭和感染。肝脾肿大的潜在并发症包括门静脉高压和静脉曲张出血，而脾脏和肝脏以外的骨髓外造血 - 根据受影响的器官 - 可能导致颅内压升高、脊髓压迫、肺动脉高压、胸腔积液、淋巴结病、皮肤损伤和/或腹部症状恶化。虽然异基因造血干细胞移植是唯一潜在的治愈性治疗方法，但它适合少数患者。JAK1/JAK2 抑制剂芦可替尼可有效改善脾肿大、MF 相关症状和生活质量指标。芦可替尼可能与中高危 MF 的生存获益相关的新证据表明，它可能具有疾病修饰作用。因此，芦可替尼可为其他（常规和新型）治疗方法提供治疗基础，以预防和有效管理特定的 MF 相关并发症。
