骨髓增殖性肿瘤中JAK2V617F突变与Ⅰ型细胞因子受体相关性研究

目的探讨促红细胞生成素受体(EPOR)、粒细胞集落刺激因子受体(G-CSFR)、血小板生成素受体(MPL)在骨髓增殖性肿瘤(MPN)中的表达情况及其与JAK2V617F突变的相关性。方法选取44例BCR/ABL阴性MPN患者包括16例真性红细胞增多症(PV)、14例原发性血小板增多症(ET)、14例原发性骨髓纤维化(IMF)患者]、11例慢性粒细胞白血病(CML)患者和20例健康志愿者(正常对照组)。应用定量逆转录聚合酶链反应(FQ-RT-PCR)技术检测上述受检者的骨髓或外周血JAK2V617F突变及EPOR、G-CSFR、MPL的mRNA表达情况。结果在44例BCR/ABL阴性的MPN患者中有26例(59.1%)存在JAK2V617F点突变,而在11例CML患者和20例正常对照者中未检测到JAK2V617F突变。BCR/ABL阴性MPN初治患者EPOR、G-CSFR的mRNA表达水平高于正常对照组(P<0.05),而MPL的mRNA表达水平与正常对照组比较差异无统计学意义(P>0.05);CML患者EPOR、G-CSFR、MPL的mRNA表达水平均高于正常对照组(P<0.05),BCR/ABL阴性JAK2V617F突变阳性与阴性初治组患者EPOR、G-CSFR、MPL的mRNA表达无明显差异(P>0.05)。结论Ⅰ型细胞因子和(或)JAK2V617F参与了MPN的发病;Ⅰ型细胞因子受体在多种造血系统肿瘤疾病中高表达,但对MPN的发病并非决定因素。

Correlation between JAK2V617F Mutation and the Expression of Type I Cytokine Receptors in Myeloproliferative Neoplasms

Objective To investigate the expressions of erythropoietin receptor(EPOR),granulocyte colony-stimulating factor receptor(G-CSFR) and thrombopoietin receptor(MPL) in chronic myeloproliferative neoplasms(MPN) and to discuss their correlations with JAK2V617F mutation.Methods The mRNA expressions of EPOR,GCSFR,MPL and JAK2V617F mutation in marrow or peripheral blood mononuclear cells in 44 patients with BCR/ABL negative chronic myeloproliferative neoplasms(16 for PV,14 for ET,14 for IMF),11 patients with CML and 20 healthy volunteers were measured with real-time fluorescent relative-quantification PCR(FQ-PCR).The correlation between cytokine receptors and JAK2V617F mutation in MPN patients were evaluated.Results 26 in 44 patients with BCR/ABL negative MPN had JAK2V617F mutation(59.1%),while no JAK2V617F mutation was detected in 11 patients with CML and 20 normal controls.mRNA expression levels of EPOR and G-CSFR were significantly higher in patients with BCR/ABL negative MPN than those of normal controls(P<0.05),but mRNA expression level of MPL in patients with BCR/ABL negative MPN showed no statistically significant differences compared with normal controls(P>0.05).EPOR,G-CSFR and MPL mRNA expression levels were all significantly higher in patients with BCR/ABL positive CML(P<0.05).EPOR,G-CSFR and MPL mRNA expression levels were no statisticly significant in JAK2V617F mutation or not BCR/ABL negative and untreated patients(P>0.05).Conclusion Type Ⅰ cytokine receptors and or JAK2V617F are involved in MPN pathogenesis,and type I cytokine receptor have high level expression in many hemopoietic system neoplasms,but it is not the major determinant.