摘要
目的探讨干扰素α(IFN-α)在治疗JAK2V617F突变阳性的骨髓增殖性疾病中的作用机制。方法应用荧光定量PCR检测IFN-α治疗前后不同时间骨髓液JAK2V617F和PRV-1 mRNA表达水平;体外半固体集落培养检测自发性红系集落形成(EEC),流式细胞术检测体外IFN-α促凋亡作用。结果10例JAK2V617F阳性真性红细胞增多症(PV),5例特发性血小板增多症(ET),2例特发性骨髓纤维化(MF)患者在应用干扰素α治疗前骨髓液JAK2V617F mRNA平均拷贝数量为(4.35±0.98)×107,治疗1年后降低为(1.56±0.67)×103,并与PRV-1 mRNA降低呈时间依赖性负相关。同时可见IFN-α也有抑制EEC形成和促进骨髓单个粒细胞凋亡作用。结论IFN-α可以降低JAK2V617F阳性克隆比例、PRV-1的表达以及EEC的形成。JAK2V617F mRNA可作为患者骨髓液中治疗效果的分子生物学标记。
Objective To evaluate interferon alpha (IFN-α) in treatment of JAK2V617F positive myeloproliferative disorders (cMPDs). Methods Ten patients of polycythemia vera (PV), 5 of essential thrombocythemia (ET) and 2 of idiopathic myelofibrosis (IMF) with JAK2V617F mutation were treated with IFN-a. The expression levels of JAK2V617F and PRV-hnRNAs were detected by real-time fluorescent relative-quantification RT-PCR;the endogenous erythroid colony (EEC)by colony culture technique;apoptosis of bone marrow mononuclear cells by flow cytometry (FCM). Results The average copies of JAKV617F mRNA were higher in untreated patients [(4.35±0.98)× 10^7] than those treated with IFN-α for one year [(1.56±0.67)×10^3]. PRV-1 mRNA expression and EEC formation were also decreased in a dose-dependent manner after IFN-α treatment. IFN-α also induced cell apoptosis in vitro. Conclusion IFN-α can inhibit the growth of JAK2V617F positive clone and reduce the expression level of PRV-1 mRNA and EEC formation.
出处
《实用肿瘤杂志》
CAS
2008年第4期318-321,共4页
Journal of Practical Oncology