Turk J Haematol. 2022 Jan 4. doi: 10.4274/tjh.galenos.2021.2021.0607. Online ahead of print.
ABSTRACT
Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) have a high propensity for thrombosis, which has been attributed to the increased blood counts, endothelial cell (EC) dysfunction, and inflammation. The presence of the JAK2V617F mutation in the ECs of MPN patients has been confirmed, but the consequences of EC involvement by JAK2V617F in the pathogenesis of thrombosis are unclear. Endothelial microparticles (EMPs) released from EC play an important role in endothelial dysfunction and also for the intercellular exchange of biological signals and information. Several studies have revealed that the patients with JAK2V617F and a thrombosis history have an increased number of microparticles in their circulation. The current study utilized a lentiviral transduction model of JAK2 wild type (JAK2wt) or JAK2V617F encoding green fluorescent protein (GFP) into the human umbilical vein EC to determine the effect of the JAK2V617F on EC. The proteins of ECs that potentially play a role in the development of thrombosis, including endothelial protein C receptor, thrombomodulin, and tissue factor, were detected between JAK2617F, JAK2wt, and GFP-only ECs with no statistical significance after two days infection with flow cytometry analysis. Increased annexin- V uptake of JAK2617F and JAK2wt ECs compared to GFP-alone EC were detected. The EMP production in the supernatants of the EC culture was investigated. Genotyping of EMP revealed the presence of genomic DNA and RNA fragments in the EMP cargos from the cell of origin in which JAK2V617F EC released EMPs with JAK2V617F DNA fragments-a result that reveals that EMPs might regulate distant and neighboring cells via their cargo materials. This novel finding provides the first evidence for the direct effect of JAK2V617F on the ECs and their functions and suggests the role of other mechanisms in the pathogenesis of thrombosis in MPNs.
PMID:34981912 | DOI:10.4274/tjh.galenos.2021.2021.0607
