Targeting PAR1 activation in JAK2V617F-driven philadelphia-negative myeloproliferative neoplasms: Unraveling its role in thrombosis and disease progression.

Philadelphia chromosome-negative myeloproliferative neoplasms (PhMPNs) are clonal disorders marked by high morbidity and mortality, driven by uncontrolled myeloid proliferation from hematopoietic stem/progenitor cells (HSCs) and associated with a significant risk of thrombosis. This study explored the relationship between JAK2V617F and protease-activated receptor 1 (PAR1) by examining PAR1 expression and activation across various hematopoietic stem/progenitor cell (HSPC) subgroups, assessing their contribution to the hypercoagulable state in PhMPNs. We investigated the effects of thrombin, a PAR1 antagonist (vorapaxar), and a JAK2 inhibitor (ruxolitinib) on PhMPN cells.

Effect of hypoxia on HIF-1α and NOS3 expressions in CD34 cells of JAK2V617F-positive myeloproliferative neoplasms.

Purpose: Myeloproliferative neoplasms (MPN) are a heterogeneous group of hematopoietic stem-cell diseases with excessive proliferation of one or more blood cell lines. In this study, we evaluated the effect of different oxygen concentrations on HIF-1α and NOS3 gene expression to determine the effect of the bone marrow microenvironment on JAK2V617F positive Philadelphia chromosome negative (Ph) MPNs.

Patients And Methods: Peripheral blood mononuclear cells (MNC) of 12 patients with Ph MPN were collected.

Circulating CD133+/–CD34– Have Increased c- Expression in Myeloproliferative Neoplasms.

Objective: Myeloproliferative neoplasms (MPNs) are hematopoietic stem cell (HSC)-originated diseases with clonal myeloproliferation. The constitutive activation of the JAK/STAT pathway is frequently detected in patients with Philadelphia chromosome-negative (Ph–) MPNs with an acquired V617F mutation. The c- proto-oncogene is associated with malignant growth and cellular transformation, and V617F was previously shown to induce constitutive expression of c-.