Tefferi Ayalew
Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Cancer J. 2007 Nov-Dec;13(6):366-71. doi: 10.1097/PPO.0b013e318159467b.
With the discovery in the last 3 years of novel Janus kinase 2 (JAK2) and thrombopoietin receptor (MPL) mutations, the pathogenetic understanding of and clinical practice for myeloproliferative neoplasms (MPNs) have entered a new era. Each one of these newly discovered mutations, including JAK2V617F, MPLW515L, and a JAK2 exon 12 mutation, has been shown to result in constitutive activation of JAK-STAT signaling and also induce a MPN phenotype in mice. Thus, JAK2 is now considered to be a legitimate target for drug development in MPNs, and small molecule JAK2 inhibitors have already gone through successful preclinical testing, and early-phase human trials in primary myelofibrosis have already begun. Furthermore, JAK2 mutation screening has now become a front-line diagnostic test in the evaluation of both "erythrocytosis" and thrombocytosis and the 2001 World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis have now been revised to incorporate JAK2V617F mutation screening.
在过去3年中发现了新型的Janus激酶2（JAK2）和血小板生成素受体（MPL）突变，对骨髓增殖性肿瘤（MPN）的发病机制认识及临床实践进入了一个新时代。这些新发现的突变，包括JAK2V617F、MPLW515L和JAK2外显子12突变，每一个都已被证明会导致JAK-STAT信号通路的组成性激活，并且在小鼠中诱导MPN表型。因此，JAK2现在被认为是MPN药物开发的一个合理靶点，小分子JAK2抑制剂已经通过了成功的临床前测试，并且原发性骨髓纤维化的早期人体试验已经开始。此外，JAK2突变筛查现在已成为评估“红细胞增多症”和血小板增多症的一线诊断测试，并且2001年世界卫生组织真性红细胞增多症、原发性血小板增多症和原发性骨髓纤维化的诊断标准现已修订，纳入了JAK2V617F突变筛查。
