MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford.
National Institutes for Health Research Biomedical Research Centre, University of Oxford, Oxford.
Br J Haematol. 2022 Mar;196(5):1149-1158. doi: 10.1111/bjh.17850. Epub 2021 Oct 7.
Breakpoint cluster region-Abelson (BCR-ABL) negative myeloproliferative neoplasms (MPNs) are chronic myeloid neoplasms initiated by the acquisition of gene mutation(s) in a haematopoietic stem cell, leading to clonal expansion and over-production of blood cells and their progenitors. MPNs encompass a spectrum of disorders with overlapping but distinct molecular, laboratory and clinical features. This includes polycythaemia vera, essential thrombocythaemia and myelofibrosis. Dysregulation of the immune system is key to the pathology of MPNs, supporting clonal evolution, mediating symptoms and resulting in varying degrees of immunocompromise. Targeting immune dysfunction is an important treatment strategy. In the present review, we focus on the immune landscape in patients with MPNs - the role of inflammation in disease pathogenesis, susceptibility to infection and emerging strategies for therapeutic immune modulation. Further detailed work is required to delineate immune perturbation more precisely in MPNs to determine how and why vulnerability to infection differs between clinical subtypes and to better understand how inflammation results in a competitive advantage for the MPN clone. These studies may help shed light on new designs for disease-modifying therapies.
BCR-ABL 阴性骨髓增殖性肿瘤（MPN）是由造血干细胞获得基因突变引起的慢性髓系肿瘤，导致血细胞及其前体细胞的克隆性扩张和过度产生。MPN 包括一系列具有重叠但不同分子、实验室和临床特征的疾病。这包括真性红细胞增多症、原发性血小板增多症和骨髓纤维化。免疫系统的失调是 MPN 病理学的关键，支持克隆进化，介导症状，并导致不同程度的免疫功能低下。靶向免疫功能障碍是一种重要的治疗策略。在本综述中，我们重点关注 MPN 患者的免疫图谱——炎症在疾病发病机制、感染易感性和新兴治疗性免疫调节策略中的作用。需要进一步的详细研究来更精确地描绘 MPN 中的免疫失调，以确定为什么不同临床亚型对感染的易感性不同，以及更好地了解炎症如何为 MPN 克隆带来竞争优势。这些研究可能有助于为疾病修饰治疗提供新的设计思路。
