Ph染色体阴性骨髓增殖性肿瘤的治疗进展

Progress of Treatment for Ph Chromosome-Negative Myeloproliferative Neoplasms

Ph染色体阴性骨髓增殖性肿瘤(MPN)是一组起源于多能造血干细胞的恶性骨髓增殖性疾病,Janus激酶(JAK)-信号转导及转录激活因子信号转导通路等多种信号通路的异常活化可能参与MPN的发病机制,并与不同临床表型相关。近年来,针对不同信号通路的新型药物(如JAK抑制剂、鼠双微体2抑制剂、组蛋白脱乙酰酶抑制剂)的临床研究成为MPN治疗的新方向,弥补了传统药物缺乏基于发病机制治疗的不足,使提高MPN疗效、降低突变基因负荷、逆转纤维化成为可能。未来,新型药物的不断涌现有望为MPN的治疗带来新的选择。

Ph chromosome-negative myeloproliferative neoplasms(MPN)are clonal disorders involving hematopoietic stem and progenitor cells.Many abnormal signaling pathways,such as Janus kinase(JAK)-signal transduction and activator of transcription signaling pathway,may participate in the pathogenesis of MPN and are related to different clinical phenotypes.In recent years,the clinical studies for novel drugs(such as JAK inhibitors,murine double minute 2 inhibitors,and histone deacetylase inhibitors)targeting different signaling pathways have provided new directions for the treatment of MPN,which make up for the deficiency of the traditional drugs′lack of pathology-based treatments,and make it possible to improve the therapeutic effect,reduce the mutation gene load and reverse fibrosis of the MPN patients.In the future,the emergence of novel drugs are expected to bring new options for the MPN treatment.