经典Ph^(-)骨髓增殖性肿瘤的诊疗新进展

Advances in diagnosis and treatment of classical Ph^(-) myeloproliferative neoplasms

经典Ph^(-)骨髓增殖性肿瘤(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)。伴驱动基因JAK2、MPL及CALR突变是MPN的主要诊断标准之一,骨髓组织病理学特征和非驱动基因突变可以辅助进行MPN诊断和患者预后判断。第1代Janus激酶(JAK)2抑制剂芦可替尼,可快速、显著、持续缩小MPN患者脾体积,并缓解机体症状。多项Ⅲ期临床研究结果证实,第2代JAK抑制剂,如fedratinib、momelotinib和pacritinib,在PMF治疗中的疗效良好。除JAK抑制剂外,针对其他靶点的新药,如B细胞淋巴瘤/白血病(BCL)-2/BCL-xL抑制剂navitoclax、端粒酶抑制剂imetelstat和溴结构域和超末端结构蛋白(BET)抑制剂CPI-0610,也在Ph^(-)MPN患者中显示出缩小脾体积,甚至控制骨髓纤维化(MF)程度的疗效。为了提高临床医师对经典Ph^(-)MPN的认识,笔者拟就近年经典Ph^(-)MPN诊断、预后分层、治疗及疗效评价方面的最新研究进展进行阐述。

Classical Ph^(-) myeloproliferative neoplasms(MPN)include polycythemia vera(PV),essential thrombocytosis(ET)and primary myelofibrosis(PMF).Presence of driver gene mutation of JAK2,MPL or CALR is a major diagnostic criteria of MPN.Histopathological features of bone marrow and mutations in non-driver gene are also of utmost importance for assisting diagnosis and prognosis of patients.The first-generation Janus kinase(JAK)2 inhibitor ruxolitinib has been used in management of patients in terms of controlling splenomegaly and relieving constitutional symptoms rapidly and continuously.Several phase Ⅲ clinical trials have demonstrated good efficacy in patients with PMF treated by the second-generation JAK inhibitors,such as fedratinib,momelotinib and pacritinib.In addition to JAK inhibitors,new agents targeting other targets,such as B-cell lymphoma/leukemia(BCL)-2/BCL-xL inhibitor navitoclax,telomerase inhibitor imetelstat and bromodomain and extraterminal domain(BET)inhibitor CPI-0610,also show the therapeutic effects in reduction of spleen volume and improvement in degree of myelofibrosis(MF).To improve understanding of classical Ph^(-) MPN among clinicians,this article will focus on the latest research progresses of diagnosis,risk stratification,treatment and efficacy evaluation for classical Ph^(-) MPN.