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PD-1/PD-L1及Treg细胞在JAK2 V617F阳性骨髓增殖性肿瘤中的表达及意义 被引量:8

Clinical Significance and Expression of PD-1/PD-L1 and Treg Cells in JAK2 V617F Positive Myeloproliferative Neoplasms
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摘要 【目的】探讨程序性死亡受体-1(PD-1)、程序性死亡配体-1(PD-L1)及CD4+CD25+Foxp3+调节性T细胞(Treg)、CD4+/CD8+比值在JAK2 V617F突变阳性骨髓增殖性肿瘤(MPN)患者骨髓中的表达及临床意义。【方法】收集45例JAK2 V617F阳性的MPN患者,其中原发性血小板增多症(ET)17例、真性红细胞增多症(PV)13例、原发性骨髓纤维化(PMF)15例;包括初治组30例、治疗组15例。15例健康志愿者作为对照组。荧光定量聚合酶链反应(FQ-PCR)检测突变型与野生型JAK2比值。免疫组化检测患者及对照骨髓病理切片p-JAK2、PD-1、PD-L1表达情况,流式细胞术检测Treg和淋巴细胞亚群在MPN患者及对照组外周血中的变化。【结果】初治组p-JAK2、PD-1、PD-L1及Treg表达水平明显高于治疗组及对照组(P均<0.05),而CD4+/CD8+比值明显低于治疗组及对照组(P均<0.05)。JAK2 V617F突变量与PD-1及PD-L1正相关,与CD4+/CD8+负相关(r=0.593,P<0.01;r=0.723,P<0.01;r=-0.771,P<0.01)。【结论】p-JAK2、PD-1、PD-L1及Treg、CD4+/CD8+与JAK2 V617F共同参与了骨髓增殖性肿瘤发病。 【Objective】To investigate the expression and clinical significance of programmed death-1(PD-1),programmed death-ligand 1(PD-L1)and CD4^+CD25^+Foxp3^+regulatory T cells(Treg)and CD4^+/CD8^+ratios in JAK2 V617F mutation positive myeloroliferative neoplasms patients(MPN).【Methods】45 cases of JAK2 V617F positive MPN patients were selected including 17 cases of essential thrombocythemia(ET),13 cases of polycythemia vera(PV)and 15 cases of primary myelofibrosis(ET).30 cases of the newly diagnosed group and 15 cases of treatment group were from them.15 cases of healthy volunteers were selected as control group.The ratio of mutant and wild type of JAK2 was detected by fluorescence quantitative polymerase chain reaction(FQ-PCR).The expression levels of p-JAK2,PD-1 and PD-L1 in pathological tissues of bone marrow were detected by immunohistochemistry.The changes of treg cells and lymphocyte subsets in peripheral blood of MPN patients and controls were detected by flow cytometry.【Results】The expression levels of p-JAK2,PD-1,PD-L1,and Treg in the newly diagnosed group were significantly higher than that of treatment group and control group(P<0.05),while the expression levels of CD4^+/CD8^+ratio were significantly lower than treatment group and control group(P<0.05).JAK2 V617F mutation burden was positive correlation with PD-1 and PD-L1,and was negative correlation with CD4^+/CD8^+,the correlation coefficients were r=0.593,P<0.01;r=0.723,P<0.01;r=-0.771,P<0.01,respectively.【Conclusion】p-JAK2,PD-1,PD-L1,Treg,CD4^+/CD8^+and JAK2 V617F were involved in the pathogenesis of myeloroliferative neoplasms.
作者 成志勇 张丽军 付建珠 刘芳 颜晓燕 孙立娜 孙雪珊 王素云 CHENG Zhi-yong;ZHANG Li-jun;FU Jian-zhu;LIU Fang;YAN Xiao-yan;SUN Li-na;SUN Xue-shan;WANG Su-yun(Department of Hematology,The No.1 Hospital of Baoding,Baoding 071000,China;Graduate School,ChengdeMedical University,Chengde 067000,China;Department of Pathology,Baoding Children’s Hospital,Baoding071000,China;Department of Hematology,Hebei General Hospital,Shijiazhuang 050000,China)
出处 《中山大学学报(医学版)》 CAS CSCD 北大核心 2019年第1期98-103,共6页 Journal of Sun Yat-Sen University:Medical Sciences
基金 河北省科技计划项目(162777120D)
关键词 骨髓增殖性肿瘤 JAK2V617F PD-1 PD-L1 调节性T细胞 CD4^+/CD8^+ myeloproliferative neoplasms JAK2 V617F programmed death-1 programmed death-ligand 1 Treg CD4^+/CD8^+
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