Novel Pathophysiological Mechanisms of Thrombosis in Myeloproliferative Neoplasms

AbstractPurpose of ReviewThrombosis 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 FindingsRecent studies highlight that inJAK2V617F granulocytes and platelets, thrombo-inflammatory genes are upregulated. Furthermore, inJAK2V617F 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 l ead 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 p ro-coagulant and pro-adhesive proteins, such as von Willebrand factor or P-selectin inJAK2V61...
Source: Current Hematologic Malignancy Reports - Category: Hematology Source Type: research