Escalated PD-L1 expression has been identified during malignant transformation in a number of cancer types and helps cancer cells escape an effective anti-tumor immune response. The mechanisms underlying escalated production of PD-L1 in many cancers, however, are still far from clear. We studied PD-L1, STAT3 and STAT5 mRNA expression using qRT-PCR in 72 BCR/ABL1 negative myeloproliferative neoplasm (MPN) patients (39 polycythemia vera and 33 essential thrombocythemia). Furthermore, phosphorylation status of STAT3 and STAT5 was studied using immunoblotting in the same patients. All MPN patients were first screened for JAK2 (V617F) mutation by tetra-primer ARMS-PCR, followed by quantification of JAK2 (V617F) mutation burden in all V617F positive MPN patients by ASO-PCR. Patients were screened for BCR/ABL1 fusion gene transcripts to rule out Ph positive status. Our findings showed that mRNA levels of PD-L1 and STAT3 were significantly higher in JAK2 (V617F) MPN patients, while as STAT5 was insignificantly upregulated. STAT3 and STAT5 phosphorylation was seen to be higher in JAK2 (V617F) MPN patients compared to the JAK2 (WT) patients. Upregulation of PD-L1, STAT3 and STAT5 was significantly associated with JAK2 (V617F) percentage in MPN patients. PD-L1, STAT3 and STAT5 expression significantly and positively correlated with JAK2 (V617F) allele burden. In addition, significant coexpression of PD-L1 with STAT3 and STAT5 was observed in MPN patients. In summary, JAK2 (V617F) mutation is accompanied by increased PD-L1 expression and this PD-L1 over expression is mediated by JAK2 (V617F) mainly through STAT3, while as STAT5 may play a minor role.

中文翻译：

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JAK2 (V617F) 骨髓增生性肿瘤患者中的异位 PD-L1 表达是通过增加 STAT3 和 STAT5 的激活来介导的。

已经在许多癌症类型的恶性转化过程中发现了升高的 PD-L1 表达，并帮助癌细胞逃避有效的抗肿瘤免疫反应。然而，许多癌症中 PD-L1 产生增加的机制仍不清楚。我们使用 qRT-PCR 研究了 72 名 BCR/ABL1 阴性骨髓增殖性肿瘤 (MPN) 患者（39 名真性红细胞增多症和 33 名原发性血小板增多症）的 PD-L1、STAT3 和 STAT5 mRNA 表达。此外，在同一患者中使用免疫印迹研究了 STAT3 和 STAT5 的磷酸化状态。所有 MPN 患者首先通过四引物 ​​ARMS-PCR 筛查 JAK2 (V617F) 突变，然后通过 ASO-PCR 对所有 V617F 阳性 MPN 患者的 JAK2 (V617F) 突变负荷进行量化。筛查患者的 BCR/ABL1 融合基因转录物以排除 Ph 阳性状态。我们的研究结果表明，JAK2 (V617F) MPN 患者的 PD-L1 和 STAT3 的 mRNA 水平显着升高，而 STAT5 的上调不显着。与 JAK2 (WT) 患者相比，JAK2 (V617F) MPN 患者的 STAT3 和 STAT5 磷酸化水平更高。MPN 患者中 PD-L1、STAT3 和 STAT5 的上调与 JAK2 (V617F) 百分比显着相关。PD-L1、STAT3 和 STAT5 表达与 JAK2 (V617F) 等位基因负荷显着正相关。此外，在 MPN 患者中观察到 PD-L1 与 STAT3 和 STAT5 的显着共表达。总之，JAK2 (V617F) 突变伴随着 PD-L1 表达增加，而这种 PD-L1 过度表达是由 JAK2 (V617F) 主要通过 STAT3 介导的，