Yoshida Kenichi
Division of Cancer Evolution, National Cancer Center Research Institute.
Rinsho Ketsueki. 2024;65(8):784-789. doi: 10.11406/rinketsu.65.784.
Recent advances in sequencing technologies have clarified the driver gene landscape in Philadelphia chromosomenegative (Ph-) myeloproliferative neoplasms (MPNs) and progressed understanding of MPN pathogenesis. Beyond mutations in the main three drivers of MPN, namely JAK2, MPL and CALR, somatic mutations in the epigenetic regulators and RNA splicing factors have been identified and their association with transformation to myelofibrosis and acute myeloid leukemia have been determined. Clonal expansion of hematopoietic cells with driver mutations (clonal hematopoiesis) has been detected in healthy individuals, especially in elderly people. In MPN patients, however, initial driver mutations such as those in JAK2 and DNMT3A have been shown to be acquired in utero or during childhood. In this review, I will summarize the recent findings about clonal evolution in MPN and the role of driver mutations.
测序技术的最新进展已阐明了费城染色体阴性（Ph-）骨髓增殖性肿瘤（MPN）中的驱动基因格局，并推动了对MPN发病机制的理解。除了MPN的三个主要驱动基因即JAK2、MPL和CALR的突变外，还鉴定出了表观遗传调节因子和RNA剪接因子中的体细胞突变，并确定了它们与向骨髓纤维化和急性髓系白血病转化的关联。在健康个体中，尤其是老年人中，已检测到具有驱动基因突变的造血细胞克隆性扩增（克隆性造血）。然而，在MPN患者中，最初的驱动基因突变，如JAK2和DNMT3A中的突变，已被证明是在子宫内或儿童期获得的。在这篇综述中，我将总结MPN中克隆进化的最新发现以及驱动基因突变的作用。
