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干扰素对JAK2 V617F阳性骨髓增殖性肿瘤PD-1/PD-L1及Treg表达的影响

Effects of Interferon on PD-1/PD-L1 and Treg Expression in JAK2 V617F-positive Myeloproliferative Neoplasms

  • 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1×106 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。1×106 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。

     

    Abstract:
    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.

     

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