Ikeda Kazuhiko
Department of Blood Transfusion and Transplantation Immunology, Fukushima Medical University School of Medicine.
Rinsho Ketsueki. 2022;63(9):1107-1114. doi: 10.11406/rinketsu.63.1107.
Vascular diseases are a feature of myeloproliferative neoplasms (MPNs) with a driver mutation, such as JAK2V617F. There is growing evidence that clonal hematopoiesis with JAK2V617F (JAK2V617F-CH) is often complicated with vascular diseases, even in the absence of MPN onset. Such vascular diseases associated with the MPN driver mutation include arterial/venous thrombosis, atherosclerotic coronary artery disease and aortic aneurysm, and pulmonary hypertension. Murine studies have recently revealed mechanisms by which hematopoietic cells activated by the MPN driver mutation may promote thrombosis and vascular remodeling in deep vein stenosis, atherosclerosis, and pulmonary hypertension models. Furthermore, MPN driver mutations mediate various downstream molecules of JAK-STAT activation in neutrophils and macrophages, such as inflammatory cytokines, which may be candidates for preventing and treating vascular diseases in MPNs and JAK2V617F-CH.
血管疾病是具有驱动突变（如JAK2V617F）的骨髓增殖性肿瘤（MPN）的一个特征。越来越多的证据表明，携带JAK2V617F的克隆性造血（JAK2V617F-CH）常伴有血管疾病，即使在没有MPN发病的情况下也是如此。与MPN驱动突变相关的此类血管疾病包括动脉/静脉血栓形成、动脉粥样硬化性冠状动脉疾病和主动脉瘤，以及肺动脉高压。最近的小鼠研究揭示了在深静脉狭窄、动脉粥样硬化和肺动脉高压模型中，由MPN驱动突变激活的造血细胞促进血栓形成和血管重塑的机制。此外，MPN驱动突变介导中性粒细胞和巨噬细胞中JAK-STAT激活的各种下游分子，如炎性细胞因子，这些可能是预防和治疗MPN和JAK2V617F-CH中血管疾病的候选药物。
