Plasma proteome screen of individuals with elevated blood counts to identify diagnostic signatures and biomarkers inherent to patients with myeloproliferative neoplasms

BackgroundThe Philadelphia negative myeloproliferative neoplasms (MPN), including essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF), are characterized by myeloid cell proliferation, thrombosis and inflammation. Suspicion of MPN arises from increased blood count in one or more lineages; however, knowledge on the MPN plasma proteome including biomarkers measurable in blood, are lacking. Comparing the plasma proteome of MPN patients to subjects with elevated blood counts but without MPN diagnosis, may provide an increased understanding of the MPN disease biology as well as diagnostic biomarkers measurable in blood. Patients and methodsWe performed plasma proteome profiling in 87 patients referred to the Department of Hematology due to elevated blood counts. Of these, 55 were diagnosed with MPN and 32 did not fulfill MPN diagnostic criteria and thus constituted the non-MPN control group. ResultsThe frequency of thrombosis was equal between the groups. We found 189 differentially expressed proteins between MPN and non-MPN, enriched for Hemostasis and Platelet activation proteins. Using Lasso multiple regression, we identified SORT1, GP1BA, PSPN, MMP1 and BAG6 separating MPN from non-MPN individuals, and TFRC and SEMA7A specific for MPN subtype PV. Interestingly, TFRC alone had a diagnostic accuracy for identifying PV of 89.3%, and when combined with serum erythropoietin it increased to 99.3%. Only two proteins, IL-6 and GH1, were increased in JAK2 mutant MPN compared to JAK2 wildtype MPN. The same trend was seen for JAK2 mutant ET compared to JAK2 wildtype ET, indicating that IL-6 is induced by JAK STAT activation. However, IL-6 levels did not differ between MPN and non-MPN patients. Discussion/conclusionIn conclusion, hemostasis and platelet activation are inherent to MPN disease whereas little difference was found in proinflammatory cytokines between MPN and non-MPN groups. We demonstrate novel potential blood biomarkers for MPN and MPN subtypes, in particular TFRC for identifying PV patients.