Gotoh Akihiko
Department of Hematology, Tokyo Medical University, 6-7-1, Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan.
Int J Hematol. 2022 May;115(5):616-618. doi: 10.1007/s12185-022-03344-6. Epub 2022 Apr 10.
Clinical studies of Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) have progressed greatly with the discovery of mutations in three driver genes: JAK2, MPL, and calreticulin. Other genes that may play important roles in pathogenesis and progression of MPN have also been identified. Several prognostic prediction systems based on various risk factors including these genetic factors have been developed and utilized in clinical practice. All mutations of the three driver genes result in JAK2 activation, and JAK inhibitors have indeed improved clinical outcomes for primary myelofibrosis and polycythemia vera. However, they have minimal ability to inhibit clonogenic growth, far below that of ABL tyrosine kinase inhibitors in chronic myeloid leukemia. Therefore, hematopoietic stem cell transplantation (HSCT), which still has a high mortality rate, remains the only curative treatment for MPN. Efforts are being made to advance the treatment of MPN by refining HSCT methods, combining JAK inhibitors with other molecularly targeted agents, and reviewing the safety and clonogenic inhibitory effects of interferon-alfa.
随着三种驱动基因JAK2、MPL和钙网蛋白突变的发现，费城染色体阴性骨髓增殖性肿瘤（MPN）的临床研究取得了很大进展。其他可能在MPN发病机制和进展中起重要作用的基因也已被确定。基于包括这些遗传因素在内的各种危险因素的几种预后预测系统已被开发并应用于临床实践。三种驱动基因的所有突变都会导致JAK2激活，JAK抑制剂确实改善了原发性骨髓纤维化和真性红细胞增多症的临床结局。然而，它们抑制克隆生长的能力极小，远低于慢性髓性白血病中ABL酪氨酸激酶抑制剂的能力。因此，造血干细胞移植（HSCT），其死亡率仍然很高，仍然是MPN唯一的治愈性治疗方法。目前正在努力通过改进HSCT方法、将JAK抑制剂与其他分子靶向药物联合使用以及审查α-干扰素的安全性和克隆抑制作用来推进MPN的治疗。
