摘要
目的探讨干扰素-alpha-2b(IFN-α2b)对JAK2 V617F阳性骨髓增殖性肿瘤(MPN)患者中程序性死亡受体-1(PD-1)、程序性死亡配体-1 (PD-L1)及CD4^+CD25^+Foxp3^+调节性T细胞(Treg)表达的影响及临床意义。方法收集JAK2 V617F阳性MPN患者61例,包括初治组41例、IFN-α2b治疗组20例,健康对照组20例。应用荧光定量PCR检测JAK2 V617F/JAK2突变率,流式细胞术检测PD-1、PD-L1、Treg的表达情况。选取15例患者骨髓及外周血标本进行体外细胞培养,应用1×10~6 U/L IFN-α2b作用48 h后检测PD-1、PD-L1及Treg表达情况。结果初治组的JAK2 V617F、PD-1、PD-L1及Treg表达明显高于IFN-α2b治疗组及对照组(均P<0.05)。JAK2 V617F突变量≥50%患者骨髓髓系细胞PD-1、PD-L1及外周血Treg细胞均明显高于突变量<50%患者(均P<0.05)。相关性分析结果显示JAK2 V617F突变量与骨髓髓系细胞PD-1、PD-L1和淋巴细胞PD-1呈正相关,与Treg表达无相关性。1×10~6 U/L IFN-α2b作用48 h后能够体外抑制MPN原代细胞PD-1、PD-L1及Treg的表达(P<0.05)。结论 PD-1、PD-L1及Treg共同参与了MPN的发病过程,干扰素能够不同程度抑制MPN JAK2 V617F、PD-1、PD-L1及Treg表达,进而抑制MPN的进展。
Objective To explore the effect of interferon-alpha-2b(IFN-alpha 2b)on the expression of programmed death receptor-1(PD-1),programmed death ligand-1(PD-L1)and CD4+CD25+Foxp3+regulatory T cell(Treg)in JAK2 V617F-positive myeloproliferative neoplasms(MPN)and related clinical significance.Methods We collected 61 cases of JAK2 V617F-positive MPN patients,including 41 cases as the newly diagnosed group,20 cases as the IFN-α2b treatment group and 20 healthy volunteers as control group.JAK2 V617F/JAK2 ratio was detected by fluorescence quantitative polymerase chain reaction(FQ-PCR).The expression levels of PD-1 and PD-L1 in bone marrow and Treg in peripheral blood were detected by flow cytometry.The bone marrow and peripheral blood samples from 15 patients were selected and treated with 1×106U/L IFN-α2b for 48h;and then the expression levels of PD-1,PD-L1 and Treg were detected.Results The expression levels of JAK2 V617F,PD-1,PD-L1 and Treg in the newly diagnosed group were significantly higher than those in IFN-α2b treatment group and control group(P<0.05).The expression levels of PD-1,PD-L1 and Treg in the patients with JAK2 V617F/JAK2 ratio≥50%were significantly higher than those with mutation rate<50%(P<0.05).JAK2 V617F burden was positively correlated with PD-1,PD-L1 in bone marrow and PD-1 in lymphocyte,while not correlated with Treg.The expression of PD-1,PD-L1 and Treg in primary MPN cells were inhibited by IFN-α2b after 48 hours(P<0.05).Conclusion PD-1,PD-L1 and Treg participate in the pathogenesis of MPN together.Interferon could inhibit the progress of MPN via inhibiting the expression of JAK2 V617F,PD-1,PD-L1 and Treg.
作者
张丽军
齐峰
成志勇
张朝
吴士杰
郭艳涛
孙丽娜
彭占仙
梁文同
ZHANG Lijun;QI Feng;CHENG Zhiyong;ZHANG Zhao;WU Shijie;GUO Yantao;SUN Li’na;PENG Zhanxian;LIANG Wentong(Graduate School,Chengde Medical University,Chengde 067000,China;Department of Hematology,The No.1 Hospital of Baoding,Baoding 071000,China;Department of Pathology,Shijiazhuang City Luancheng People’s Hospital,Shijiazhuang 050000,China)
出处
《肿瘤防治研究》
CAS
CSCD
2019年第1期63-67,共5页
Cancer Research on Prevention and Treatment
