JAK2 V617F驱动的骨髓增生性肿瘤（MPNs）可以通过PD-L1上调和HLA I级途径下调来逃避免疫监视。为了补充这些数据，我们评估了JAK2 V617F + MPNs中主要组织相容性复合体I级相关基因（MICA和MICB）的作用。通过高分辨率基因分型，我们确定了两个保护性等位基因，分别是MICA * 008:01和MICA * 016。MPN患者的可溶性sMICA分子水平显著较高。外周血JAK2 V617F + 嗜中性粒细胞表面的MICB表达更高，但与正常粒细胞相比，在MICA和MICB转录本数量方面并没有区别。与正常CD34 +造血干细胞相比，JAK2 V617F + CD34 +细胞中的MICA和MICB基因显著下调。这些数据表明MICA和MICB基因在MPNs发病机制中作用较小但显著。MICA靶向方法也可能对部分患者有临床益处。© 2023 John Wiley＆Sons A / S。由John Wiley＆Sons Ltd.发布。

JAK2 V617F-driven myeloproliferative neoplasms (MPNs) can escape immune surveillance through PD-L1 up-regulation and HLA class I pathway down-regulation. To complement these data we assessed the role of major histocompatibility complex class I-related genes (MICA and MICB) in JAK2 V617F+ MPNs. Using high resolution genotyping we identified two protective alleles, MICA*008:01 and MICA*016. MPN patients had significantly higher levels of soluble sMICA molecules. Peripheral blood JAK2 V617F+ granulocytes had higher surface expression of MICB but did not differ in the amount of MICA and MICB transcripts from normal granulocytes. MICA and MICB genes were significantly down-regulated in JAK2 V617F+ CD34+ cells from primary myelofibrosis patients in comparison to normal CD34+ hematopoietic stem cells. These data suggest minor but significant role of MICA and MICB genes in the pathogenesis of MPNs. It is also possible that MICA targeting approaches could be of clinical benefit for some of those patients.© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.