A Specific Host/Microbial Signature of Plasma-Derived Extracellular Vesicles Is Associated to Thrombosis and Marrow Fibrosis in Polycythemia Vera

SIMPLE SUMMARY: Patients with polycythemia vera, a myeloproliferative neoplasm, are at increased risk of thrombosis and progression to myelofibrosis. However, no disease-specific risk factors have been identified so far. Extracellular vesicles, released from a broad variety of cells, are receiving increasing attention for their effects on cell-to-cell communication. In addition, they play a role in cancer and thrombosis. Interestingly, circulating microbial components/microbes have been recently indicated as potential modifiers of inflammation and coagulation. Here, we identified a signature of thrombosis history and marrow fibrosis by analyzing the phenotype and the microbial DNA cargo of the circulating extracellular vesicles after isolation from the plasma of patients with polycythemia vera. These data may support the role of extracellular vesicles as liquid biomarkers of aggressive disease, thus contributing to refining the prognosis of polycythemia vera. ABSTRACT: Polycythemia vera is a myeloproliferative neoplasm with increased risk of thrombosis and progression to myelofibrosis. However, no disease-specific risk factors have been identified so far. Circulating extracellular vesicles (EVs) are mostly of megakaryocyte (MK-EVs) and platelet (PLT-EVs) origin and, along with phosphatidylethanolamine (PE)-EVs, play a role in cancer and thrombosis. Interestingly, circulating microbial components/microbes have been recently indicated as potential modifiers of inflammation and coagulation. Here, we investigated phenotype and microbial DNA cargo of EVs after isolation from the plasma of 38 patients with polycythemia vera. Increased proportion of MK-EVs and reduced proportion of PLT-EVs identify patients with thrombosis history. Interestingly, EVs from patients with thrombosis history were depleted in Staphylococcus DNA but enriched in DNA from Actinobacteria members as well as Anaerococcus. In addition, patients with thrombosis history had also lower levels of lipopolysaccharide-associated EVs. In regard to fibrosis, along with increased proportion of PE-EVs, the EVs of patients with marrow fibrosis were enriched in DNA from Collinsella and Flavobacterium. Here, we identified a polycythemia-vera-specific host/microbial EV-based signature associated to thrombosis history and marrow fibrosis. These data may contribute to refining PV prognosis and to identifying novel druggable targets.