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TRP X3 Platelet and Leukocyte Dysfunction in Essential Thrombocythemia

Funding period: 01.04.2016 – 31.03.2019

Project Summary

Essential thrombocythemia (ET) is a clonal myeloproliferative neoplasm (MPN). Despite almost normal life expectancy, the disease is associated with a high risk of vascular events including ischemic stroke, acute myocardial infarction and venous thromboembolism, which in turn result in severe comorbidity. The underlying pathomechanisms leading to the multitude of clinical manifestations are incompletely understood. Based on our hypothesis that platelet dysfunction rather than platelet count contributes to the clinical heterogeneity, we aim to investigate the hemostatic and inflammatory platelet activation potential from patients with ET in a comprehensive approach. Patients with reactive thrombocytosis will serve as controls. Besides classical platelet function parameters, we will analyze the quantitative phospho- and thiol-redox-proteome, cytokine expression profiles as well as leukocyte function and platelet-leukocyte interactions in vitro. These functional studies will be complemented by platelet transcriptome analysis to identify additionally relevant genetic signatures. The findings will help us to identify pathomechanisms in relation to the known thromboembolic and/or hemorrhagic risk and common somatic mutations and help to define predictive markers for clinical manifestations in patients with ET. Patients will be closely monitored clinically and by platelet and leukocyte function analysis. They will be followed at least until the end of the study. We expect that this proof-of-concept study will be the basis for a large-scale study to prospectively identify individual risk factors in ET patients and also to provide treatment strategies to prevent vascular events and their associated comorbidity.

Principle Investigators

Prof. Dr. Kerstin Jurk
Prof. Dr. Kerstin Jurk
Funktionen Principal Investigator
06131 17-8278

Platzhalter-Bild
MD Thomas Kindler
Funktionen Med. Dpt. III
06131 17-5046

Staff

MD Professor Bernhard Lämmle
MD Professor Bernhard Lämmle
Funktionen Guest Professor CTH, Emeritus Professor and Director of Hematology, University of Bern

 Kathrin Groß (neé Schwierczek)
Kathrin Groß (neé Schwierczek)
Funktionen Technician
06131 17-8296