Hematology and Medical Oncology Department, Hospital Universitario Morales-Meseguer, Centro Regional de Hemodonación, IMIB-Arrixaca, 30120 Murcia, Spain.
CIBERER CB15/00055, 28029 Murcia, Spain.
Int J Mol Sci. 2021 Jan 24;22(3):1143. doi: 10.3390/ijms22031143.
Thrombosis is a major cause of morbimortality in patients with chronic Philadelphia chromosome-negative myeloproliferative neoplasms (MPN). In the last decade, multiple lines of evidence support the role of leukocytes in thrombosis of MPN patients. Besides the increase in the number of cells, neutrophils and monocytes of MPN patients show a pro-coagulant activated phenotype. Once activated, neutrophils release structures composed of DNA, histones, and granular proteins, called extracellular neutrophil traps (NETs), which in addition to killing pathogens, provide an ideal matrix for platelet activation and coagulation mechanisms. Herein, we review the published literature related to the involvement of NETs in the pathogenesis of thrombosis in the setting of MPN; the effect that cytoreductive therapies and JAK inhibitors can have on markers of NETosis, and, finally, the novel therapeutic strategies targeting NETs to reduce the thrombotic complications in these patients.
血栓形成是慢性费城染色体阴性骨髓增殖性肿瘤(MPN)患者发病和死亡的主要原因。在过去十年中,多项证据支持白细胞在 MPN 患者血栓形成中的作用。除了细胞数量增加外,MPN 患者的中性粒细胞和单核细胞还表现出促凝激活表型。中性粒细胞一旦被激活,就会释放由 DNA、组蛋白和颗粒蛋白组成的结构,称为细胞外中性粒细胞陷阱(NETs),除了杀死病原体外,NETs 还为血小板激活和凝血机制提供了理想的基质。在此,我们回顾了与 NETs 在 MPN 背景下血栓形成发病机制中的作用相关的已发表文献;细胞减少治疗和 JAK 抑制剂对 NETosis 标志物的影响,最后是针对 NETs 的新型治疗策略,以减少这些患者的血栓并发症。