Novel Pathophysiological Mechanisms of Thrombosis in Myeloproliferative Neoplasms.
Novel Pathophysiological Mechanisms of Thrombosis in Myeloproliferative Neoplasms.
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骨髓增生性肿瘤血栓形成的新病理生理机制。
DOI：
10.1007/s11899-021-00630-8
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发表时间：
2021-06
影响因子：
2.9
通讯作者：
Beckman JD
中科院分区：
文献类型：
--
作者：
Reeves BN;Beckman JD
血栓形成仍然是BCR/ABL阴性骨髓增生性肿瘤（MPN）发病和死亡的主要原因。在MPN中，循环血细胞在数量和质量上都增加，导致血栓形成风险增加。在此，我们回顾了最近阐明的MPN血栓形成机制，并讨论了目前正在研究的药物对MPN的影响。最近的研究强调，在JAK2V617F中，粒细胞和血小板的血栓炎性基因上调。此外，在JAK2V617F粒细胞中，整合素CD11b、组织因子和白细胞碱性磷酸酶的蛋白表达均升高。总的来说，骨髓细胞，即中性粒细胞，可能以几种方式起作用，例如通过β1整合素与VCAM1结合增加粘附，增加浸润，增强挤压中性粒细胞胞外陷阱的诱导能力。非髓系炎症细胞也可能通过分泌细胞因子而起作用。关于红细胞的数量、硬度、粘附性和微泡的产生可能导致血管阻力增加以及促进滚动和粘附的细胞间相互作用增加。血小板也可能以类似的方式起作用。最后，血管系统也越来越受到重视，因为一些研究表明内皮细胞中促凝和促粘附蛋白的表达增加，如血管性血液病因子或p -选择素，JAK2V617F。随着分子诊断的出现，MPN疗法正在超越细胞减少。我们对MPN中促炎和血栓形成病理生理的进一步了解，为评估正在开发的MPN治疗方法以减少血栓形成提供了合理的基础。
Thrombosis remains a leading cause of morbidity and mortality in BCR/ABL negative myeloproliferative neoplasms (MPN). Circulating blood cells are both increased in quantity and are qualitatively abnormal in MPN, resulting in increased thrombotic risk. Herein, we review recently elucidated mechanisms of MPN thrombosis and discuss implications of drugs currently under investigation for MPN. Recent studies highlight that in JAK2V617F granulocytes and platelets thrombo-inflammatory genes are upregulated. Furthermore, in JAK2V617F granulocytes, protein expression of integrin CD11b, tissue factor, and leukocyte alkaline phosphatase are all increased. Overall, myeloid cells, namely neutrophils, may contribute in several ways, such as through increased adhesion via β1 integrin binding to VCAM1, increased infiltration, and enhanced inducibility to extrude neutrophil extracellular traps. Non-myeloid inflammatory cells may also contribute via secretion of cytokines. With regard to red blood cells- number, rigidity, adhesion and generation of microvesicles may lead to increased vascular resistance as well as increased cell-cell interactions that promote rolling and adhesion. Platelets may also contribute in similar fashion. Last, the vasculature is also increasingly appreciated as several studies have demonstrated increased endothelial expression of pro-coagulant and pro-adhesive proteins, such as von Willebrand factor or P-selectin, JAK2V617F endothelial cells. With advent of molecular diagnostics, MPN therapeutics are advancing beyond cytoreduction. Our increased understanding of pro-inflammatory and thrombotic pathophysiology in MPNs provides a rational basis for evaluation of in-development MPN therapeutics to reduce thrombosis.
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影响因子：
6.5
作者：
Burger, Patrick;Kostova, Elena;van Bruggen, Robin
通讯作者：
van Bruggen, Robin
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