Edahiro Yoko
Department of Hematology, Juntendo University School of Medicine.
Rinsho Ketsueki. 2015 Aug;56(8):949-55. doi: 10.11406/rinketsu.56.949.
After the discovery of the JAK2V617F mutation in 2005, followed by the discovery of the MPL and JAK2 exon 12 mutations, and the CALR mutation in 2013, the majority of patients with Philadelphia negative myeloproliferative neoplasms (MPN) have been shown to display one of these somatic mutations. In regards to the pathogenesis of MPN, the CALR mutation has been shown to activate the JAK2 downstream cascade. However, the mechanism has yet to be elucidated. Nevertheless, these investigations have changed our understanding of MPN, especially in terms of diagnosis and treatment. Reports on the clinical effects of the different somatic mutations have revealed that MPN patients with CALR-mutated ET are less likely to have thrombosis, and that PMF patients with the CALR mutation have better overall survival. Hereafter, evaluations of the status of these gene mutations are necessary for the diagnosis of MPN, and it is important to consider how to put these genetic data to the best possible practical use.
2005年发现JAK2V617F突变后，紧接着发现了MPL和JAK2第12外显子突变，以及2013年发现的CALR突变，结果显示大部分费城阴性骨髓增殖性肿瘤（MPN）患者存在这些体细胞突变之一。关于MPN的发病机制，CALR突变已被证明可激活JAK2下游级联反应。然而，其机制尚未阐明。尽管如此，这些研究改变了我们对MPN的认识，尤其是在诊断和治疗方面。关于不同体细胞突变临床效应的报告显示，CALR突变型ET的MPN患者发生血栓形成的可能性较小，而CALR突变型PMF患者的总生存期更好。此后，评估这些基因突变状态对于MPN的诊断是必要的，并且考虑如何将这些遗传数据发挥出最佳实际用途也很重要。
