Platelet Proteome Links Metabolism to Reactivity in Essential Thrombocythemia

Essential thrombocythemia (ET) is a myeloproliferative neoplasm in which JAK2, CALR, and MPL mutations are associated with distinct clinical phenotypes. Here, we analyzed the platelet proteome of ET patients by MS, combined with functional assays, to investigate platelet activation. Compared with healthy controls, ET platelets showed altered abundance of mitochondrial and metabolic proteins, including reduced levels of tricarboxylic acid cycle enzymes and a relative enrichment of glycolytic signatures. Acetylsalicylic acid decreased the abundance of metabolic proteins in CALR Type1 platelets, whereas JAK2 V617F platelets showed only minor, heterogeneous increases restricted to a subset of proteins and samples. In functional assays, JAK2 V617F platelets showed aggregation responses similar to or lower than those of healthy controls, whereas untreated CALR Type2 platelets showed higher CD62P expression, indicating a more activated phenotype than the other ET groups. These findings indicate that ET platelets display mutation-associated proteomic and functional differences and suggest that an altered metabolic state may contribute to platelet reactivity.