{"title":"Novel Pathophysiological Mechanisms of Thrombosis in Myeloproliferative Neoplasms.","authors":"Brandi N Reeves, Joan D Beckman","doi":"10.1007/s11899-021-00630-8","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose of review: </strong>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 qualitatively abnormal in MPN, resulting in an increased thrombotic risk. Herein, we review recently elucidated mechanisms of MPN thrombosis and discuss implications of drugs currently under investigation for MPN.</p><p><strong>Recent findings: </strong>Recent studies highlight that in JAK2<sup>V617F</sup> granulocytes and platelets, thrombo-inflammatory genes are upregulated. Furthermore, in JAK2<sup>V617F</sup> 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 a similar fashion. Lastly, 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 in JAK2<sup>V617F</sup> endothelial cells. With the advent of molecular diagnostics, MPN therapeutics are advancing beyond cytoreduction. Our increased understanding of pro-inflammatory and thrombotic pathophysiology in MPN provides a rational basis for evaluation of in-development MPN therapeutics to reduce thrombosis.</p>","PeriodicalId":10852,"journal":{"name":"Current Hematologic Malignancy Reports","volume":null,"pages":null},"PeriodicalIF":2.7000,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11899-021-00630-8","citationCount":"14","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Hematologic Malignancy Reports","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11899-021-00630-8","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2021/4/19 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 14
Abstract
Purpose of review: 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 qualitatively abnormal in MPN, resulting in an increased thrombotic risk. Herein, we review recently elucidated mechanisms of MPN thrombosis and discuss implications of drugs currently under investigation for MPN.
Recent findings: 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 a similar fashion. Lastly, 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 in JAK2V617F endothelial cells. With the advent of molecular diagnostics, MPN therapeutics are advancing beyond cytoreduction. Our increased understanding of pro-inflammatory and thrombotic pathophysiology in MPN provides a rational basis for evaluation of in-development MPN therapeutics to reduce thrombosis.
期刊介绍:
his journal intends to provide clear, insightful, balanced contributions by international experts that review the most important, recently published clinical findings related to the diagnosis, treatment, management, and prevention of hematologic malignancy.
We accomplish this aim by appointing international authorities to serve as Section Editors in key subject areas, such as leukemia, lymphoma, myeloma, and T-cell and other lymphoproliferative malignancies. Section Editors, in turn, select topics for which leading experts contribute comprehensive review articles that emphasize new developments and recently published papers of major importance, highlighted by annotated reference lists. An international Editorial Board reviews the annual table of contents, suggests articles of special interest to their country/region, and ensures that topics are current and include emerging research. Commentaries from well-known figures in the field are also provided.