Abdel-Wahab Omar I, Levine Ross L
The Leukemia Service, Department of Medicine, and the Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
Annu Rev Med. 2009;60:233-45. doi: 10.1146/annurev.med.60.041707.160528.
Primary myelofibrosis (PMF) is a clonal stem cell disorder that manifests clinically as anemia, splenomegaly due to extramedullary hematopoiesis, leukoerythroblastosis, and constitutional symptoms, which are the clinical hallmarks of PMF. Within the past three years it has been determined that a single, recurrent, somatic mutation in the gene encoding the cytoplasmic tyrosine kinase Janus kinase 2 (JAK2) occurs in the majority of patients with PMF, and more recently, activating mutations in the gene encoding the thrombopoietin receptor MPL have also been identified in a subset of PMF patients. These discoveries have yielded important insights into the pathogenesis of PMF and have brought about the first opportunity for rationally targeted therapy for this disorder. Here we present an updated review of the pathogenesis, definition, and treatment of PMF in light of the discovery of JAK2 and MPL mutations, as well as other recent work in the myeloproliferative neoplasm field.
原发性骨髓纤维化（PMF）是一种克隆性干细胞疾病，临床上表现为贫血、由于髓外造血导致的脾肿大、幼稚粒-幼红细胞血象以及全身症状，这些都是PMF的临床特征。在过去三年中，已确定大多数PMF患者存在编码细胞质酪氨酸激酶Janus激酶2（JAK2）的基因中的单一、复发性体细胞突变，最近，在一部分PMF患者中还发现了编码血小板生成素受体MPL的基因中的激活突变。这些发现为PMF的发病机制提供了重要见解，并为这种疾病带来了首次合理靶向治疗的机会。在此，我们根据JAK2和MPL突变的发现以及骨髓增殖性肿瘤领域的其他最新研究成果，对PMF的发病机制、定义和治疗进行更新综述。
