Figure 2.

Pathogenesis of fibrosis: constitutive activation of JAK-STAT pathway in the MPN stem cell cohort leads to cytokine independent growth of megakaryocytes. Emperipolesis of neutrophils occurs that leads to release of TGF-β, PDGF and bFGF from alpha granules present in megakaryocytes. These cytokines cause fibrosis and angiogenesis and also lead to osteosclerosis by causing the stromal cells to release osteoprotegerin. MPN, myeloproliferative neoplasm; TGF-β, transforming growth factor beta; PDGF, platelet derived growth factor; FGF, basic fibroblast growth factor.