Evaluation of the mechanisms involved in static and flow cell interactions of blood outgrowth endothelial cells (BOECs) from patients with negative BCR-ABL1 myeloproliferative neoplasms

• Grant number: 19/13839-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2019
• End date: June 30, 2020
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Margareth Castro Ozelo
• Grantee: Lauanda Oliveira da Silva Monteiro
• Host Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 14/00984-3 - Red blood cell disorders: pathophysiology and new therapeutic approaches, AP.TEM

Abstract

Polycythemia vera (PV) is the most frequent myeloproliferative neoplasm, characterized by the spontaneous formation of erythroid colonies in vitro, independent of erythropoietin stimulus. It has been recently demonstrated to be associated with the JAK2 V617F point-mutation in the majority of patients. Erythrocytosis is the most common finding in this disease, leading to a series of complications, such as thromboembolic events, most commonly of the mesenteric artery and central nervous system. It has been recently demonstrated that JAK2 V617F positive erythrocytes from patients with PV have an increased expression of the Lu/BCAM (Lutheran/basal cell-adhesion molecule) protein, a receptor for the 5± chain laminin present in endothelial cells, which could be involved in the increased cellular adhesiveness in these patients and with thromboembolic events. In this study, we intend to evaluate the static and flow adhesive properties of red blood cells from patients with PV to the blood outgrowth endothelial cells (BOECs) isolated from these patients, compared to the ones extracted from healthy patients. Similar adhesion assays will be conducted with RBCs extracted from healthy individuals and BOECs from patients with PV We will evaluate the expression of proteins involved in theses cellular interactions, as well as possible signaling pathways that may be involved in this phenomenon. We will try to correlate clinical findings, JAK2 genotype e the pattern of in vitro adhesiveness observed.