August 14, 2024
Myeloproliferative neoplasms (MPNs) are chronic bone marrow malignancies characterized by clonal proliferation of hematopoietic precursors and elevated cell counts in peripheral blood.1 Patients with MPN are at risk of progression to myelofibrosis or acute leukemia and experience a substantial burden of microvascular symptoms.2,3 However, thrombosis (both arterial and venous) represents the leading cause of morbidity and mortality for patients with polycythemia vera (PV) and essential thrombocythemia (ET).4-6
Translational studies have indicated that the platelet proteome influences pathways relating to immune response, inflammation, and malignancy.7,8 Thrombocytosis and platelet hyperactivity are hallmarks of MPN;9 however, platelet count in isolation is not predictive of clinical outcome, and conventional antiplatelet therapy does not fully mitigate thrombotic risk.10 A comprehensive picture of the MPN platelet molecular profile is lacking, and to date, no studies have evaluated the unbiased platelet proteome in a sizable clinical cohort of affected patients. Here, we performed untargeted quantitative profiling of the platelet proteome in a large (n = 140) cohort of patients with PV and ET.
Using standardized platelet isolation protocols (supplemental Methods), we prepared purified platelets from peripheral blood samples of patients with an established diagnosis of MPN (World Health Organization defined, n = 59 ET, n = 41 PV) and a cohort of healthy controls (n = 40) recruited across 2 sites: Hospital Papa Giovanni XXIII, Bergamo, Italy and Mater Misericordiae University Hospital, Dublin, Ireland. Pertinent clinical features are shown in Figure 1 (and listed in supplemental Table 1). Interpatient variability, including age, sex, and treatment, as well as experimental batch effects, were adjusted as confounding factors in downstream expression analyses (supplemental Methods). Focusing on the most prothrombotic subtypes of MPNs, we hypothesized that the platelet proteome differs in MPN, and its characterization would offer insights into the underlying pathobiology and possible mechanisms underlying the associated clinical complications.