端粒酶抑制剂伊美司他治疗骨髓增殖性肿瘤的研究进展与展望

摘要

Myeloproliferative neoplasm (MPN) is a group of clonal disorders originated from hemopoietic stem cells.The discovery of the Janus kinase (JAK)2 V617F,MPL and calreticulin (CALR)mutations in patients with MPN marked an important advance in the understanding of the pathophysiology of MPN.New therapeutic strategies targeting those mutations have been developed.Imetelstat,a competitive inhibitor of telomerase,can suppress the telomerase activity in tumor cells,resulting in inhibition of tumor cell proliferation.Phase 2 clinical trials in patients with thrombocythemia (ET) and myelofibrosis (MF)have shown petients have obtained good hematologic response and molecular response after treatment of imetelstat.Imetelstat has great application prospect in clinical.In order to identify imetelstat in treatment of MPN,the authors review literatures on the mechanisms,clinical curative effects and other aspects of imetelstat in treatment of MPN.%骨髓增殖性肿瘤(MPN)是一组起源于造血干细胞的恶性骨髓增殖性疾病,随着Janus激酶(JAK)2 V617F、MPL、钙网蛋白(CALR)等基因突变的发现,MPN进入到一个新的分子生物学时代,而针对这些突变靶点的新药也逐步进入临床试验阶段.端粒酶抑制剂——伊美司他(imetelstat)被发现在体外可以抑制肿瘤细胞端粒酶活性,并且抑制肿瘤细胞增殖.Ⅱ期临床试验结果显示,伊美司他可使原发性血小板增多症(ET)和骨髓纤维化(MF)患者获得良好的血液学和分子学疗效,具有巨大的临床应用前景.为了更深人地了解端粒酶抑制剂伊美司他在MPN治疗中的临床应用,笔者拟就伊美司他治疗MPN的作用机制、临床疗效等进行阐述.