Passamonti Francesco, Maffioli Margherita, Caramazza Domenica, Cazzola Mario
Division of Hematology, Department of Internal Medicine, Ospedale di Circolo e Fondazione Macchi, Varese, Italy.
Oncotarget. 2011 Jun;2(6):485-90. doi: 10.18632/oncotarget.281.
Most BCR-ABL1-negative myeloproliferative neoplasms (MPN) carry an activating JAK2 mutation. Approximately 96% of patients with polycythemia vera (PV) harbors the V617F mutation in JAK2 exon 14, whereas the minority of JAK2 (V617F)-negative subjects shows several mutations in exon 12. Other mutation events as MPL, TET2, LNK, EZH2 have been described in chronic phase, while NF1, IDH1, IDH2, ASX1, CBL and Ikaros in blast phase of MPN. The specific pathogenic implication of these mutations is under investigation, but they may have a role in refinement of diagnostic criteria and in development of new prognostic models. Several trials with targeted therapy (JAK inhibitors) are ongoing mostly involving patients with PMF, post-PV MF and post-essential thrombocythemia (ET) MF. Treatment with ruxolitinib and TG101348 has shown clinically significant benefits, particularly in improvement of splenomegaly and constitutional symptoms in MF patients. On the other hand, JAK inhibitors have not thus far shown disease-modifying activity therefore any other deduction on these new drugs seems premature.
大多数BCR-ABL1阴性骨髓增殖性肿瘤（MPN）携带激活的JAK2突变。约96%的真性红细胞增多症（PV）患者JAK2外显子14存在V617F突变，而少数JAK2（V617F）阴性患者外显子12存在多种突变。MPL、TET2、LNK、EZH2等其他突变事件在慢性期已有报道，而NF1、IDH1、IDH2、ASX1、CBL和Ikaros在MPN的急变期有报道。这些突变的具体致病意义正在研究中，但它们可能在完善诊断标准和开发新的预后模型中发挥作用。几项针对靶向治疗（JAK抑制剂）的试验正在进行，主要涉及原发性骨髓纤维化（PMF）、PV后骨髓纤维化和原发性血小板增多症（ET）后骨髓纤维化患者。鲁索替尼和TG101348治疗已显示出临床显著益处，尤其是在改善骨髓纤维化患者的脾肿大和全身症状方面。另一方面，JAK抑制剂迄今为止尚未显示出疾病修饰活性，因此对这些新药的任何其他推断似乎都为时过早。
