Department of Medicine and Surgery, Anatomy Unit, University of Parma, Via Gramsci 14, 43126 Parma, Italy.
University Hospital of Parma, AOU-PR, Via Gramsci 14, 43126 Parma, Italy.
Cells. 2020 Sep 21;9(9):2136. doi: 10.3390/cells9092136.
Among hematologic malignancies, the classic Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) are considered a model of inflammation-related cancer development. In this context, the use of immune-modulating agents has recently expanded the MPN therapeutic scenario. Cytokines are key mediators of an auto-amplifying, detrimental cross-talk between the MPN clone and the tumor microenvironment represented by immune, stromal, and endothelial cells. This review focuses on recent advances in cytokine-profiling of MPN patients, analyzing different expression patterns among the three main Philadelphia-negative (Ph-negative) MPNs, as well as correlations with disease molecular profile, phenotype, progression, and outcome. The role of the megakaryocytic clone as the main source of cytokines, particularly in myelofibrosis, is also reviewed. Finally, we report emerging intriguing evidence on the contribution of host genetic variants to the chronic pro-inflammatory state that typifies MPNs.
在血液系统恶性肿瘤中，经典的费城阴性慢性骨髓增殖性肿瘤（MPN）被认为是炎症相关癌症发展的模型。在这种情况下，免疫调节药物的使用最近扩展了 MPN 的治疗范围。细胞因子是 MPN 克隆与免疫、基质和内皮细胞等肿瘤微环境之间自我放大、有害串扰的关键介质。本综述重点介绍了 MPN 患者细胞因子谱的最新进展，分析了三种主要的费城阴性（Ph-阴性）MPN 之间的不同表达模式，以及与疾病分子谱、表型、进展和预后的相关性。巨核细胞克隆作为细胞因子的主要来源的作用，特别是在骨髓纤维化中，也进行了综述。最后，我们报告了一些有趣的新证据，表明宿主遗传变异对 MPN 典型的慢性炎症状态有贡献。
