Platelet proteome reveals potential mediators of immunothrombosis and proteostasis in myeloproliferative neoplasms

Sarah Kelliher, Sara Gamba, Luisa Weiss, Zhu Shen, Marina Marchetti, Francesca Schieppati, Caitriona Scaife, Stephen Madden, Kathleen Bennett, Anne Fortune, Su Maung, Michael Fay, Fionnuala Ní Áinle, Patricia Maguire, Anna Falanga, Barry Kevane, and Anandi Krishnan

Myeloproliferative neoplasms (MPN) are chronic bone marrow malignancies characterised by clonal proliferation of hematopoietic precursors and elevated cell counts in peripheral blood. Patients with MPN are at risk of progression to myelofibrosis or acute leukemia and experience a substantial burden of
microvascular symptoms. However, thrombosis ( both arterial and venous), represents the leading
cause of morbidity and mortality for patients with PV and ET.

Translational studies have indicated that the platelet proteome influences pathways relating to immune
response, inflammation, and malignancy. Thrombocytosis and platelet hyperactivity are hallmarks of
MPN, however platelet count in isolation is not predictive of clinical outcome, and conventional
antiplatelet therapy does not fully mitigate thrombotic risk. A comprehensive picture of the MPN platelet
molecular profile is lacking and to date, no studies have evaluated the unbiased platelet proteome in a
sizeable clinical cohort of affected patients. In this present study, we performed untargeted quantitative
profiling of the platelet proteome in a large (n= 140) cohort of patients with PV and ET.

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