新型长效α干扰素治疗Ph-骨髓增殖性肿瘤的研究新进展

Advances in application of new long-acting interferon-αin treatment of Ph-myeloproliferative neoplasms

骨髓增殖性肿瘤(MPN)是一组起源于造血干细胞(HSC)的克隆性血液系统肿瘤。经典的Ph-MPN包括真性红细胞增多症(PV)、原发性血小板增多症(ET)和原发性骨髓纤维化(PMF)。α干扰素是治疗MPN的传统药物之一,但是曾因给药方式不便和不良反应较严重等问题,限制了其在临床的广泛应用。近年研究结果表明,α干扰素不仅能够诱导MPN患者获得临床症状、血液学和组织学缓解,还可以非特异性地降低JAK2 V617F、CALR等MPN驱动基因突变负荷。相较于传统α干扰素制剂,新型长效α干扰素,如聚乙二醇α干扰素(PEG-IFN-α)、聚乙二醇脯氨酸α干扰素等,不仅给药间隔时间延长,而且药物不良反应发生率和严重程度均显著降低。这使α干扰素在MPN中的应用再次受到关注。为了更深入地了解新型长效α干扰素治疗MPN的作用机制及疗效,笔者拟对近年其治疗Ph-MPN的研究现状进行阐述。

Myeloproliferative neoplasms(MPN)are clonal hematological disorders originating from aberrant neoplastic hematological stem cells(HSC).Ph-MPN include polycythemia vera(PV),essential thrombocythemia(ET)and primary myelofibrosis(PMF).Interferon-αis one of traditional drugs used in treatment of MPN.However,its widespread use was hampered by inconvenience of its ways of administration and adverse reactions.Recently,some results of clinical trials have indicated that interferon-αcan not only induce remission of constitutional symptoms,hematology,and histology in patients with MPN,but also non-specifically reduce driver mutation load of JAK2 V617F,CALR.Meanwhile,compared with traditional interferon-α,advent of new long-acting interferon-α,such as pegylated-interferon-α(PEG-IFN-α),ropeginterferon-α,etc.have prolonged interval of administration and significantly reduced adverse reactions.Attention has been paid to interferon-αin treatment of Ph-MPN again.This article summarizes advances in new long-acting interferon-αin treatment of MPN in recent years to better understand its mechanisms and curative effects.