rs2431697, a Polymorphism of Mir-146a, Is a Precozing Marker of Progression to Secondary Myelofibrosis: New Epigenetic Regulation of Jak/Stat3 Signaling

Abstract Introduction: Transformation to secondary myelofibrosis (MF) occurs as part of the natural history of polycythemia vera (PV) and essential thrombocythemia (ET), the two more indolent Ph-negative myeloproliferative neoplasms (MPN). Once transformed, survival is remarkably shorted. Chronic inflammation plays a critical role in the progression of MPN, driving clonal expansion toward end stage disease. Importantly, MPN are characterized by the production of inflammatory cytokines, by both malignant and non-malignant clone. Inflammation and cancer share a common pathway, i.e. NF-κB. Interestingly, miR-146a regulates TLR/NF-κB pathway through the inhibition of its targets, IRAK1 and TRAF…