POTENTIAL ROLE OF NOS3 PROMOTER POLYMORPHISM (−786T>C / C786T) IN THE PATHOGENESIS OF CHRONIC MYELOPROLIFERATIVE NEOPLASMS

Abstract

Chronic myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by dysregulated proliferation of one or more myeloid cell lineages. While driver mutations (JAK2, CALR, MPL) are central, additional genetic and environmental modifiers likely influence disease initiation, progression, and complications. Endothelial nitric oxide synthase (NOS3), via its product nitric oxide (NO), modulates vascular tone, hematopoietic niche microenvironment, and regulation of oxidative stress and inflammation. The promoter polymorphism −786T>C (aka C786T, rs2070744) is known in other diseases to influence NOS3 expression and NO bioavailability. In this review and hypothesis article, we explore mechanistic rationales by which the −786T>C variant might contribute to the pathogenesis, vascular complications, and disease progression of MPNs. We survey what is known about NOS3 biology, the functional impact of −786T>C, and analogous disease associations, and propose testable models and research strategies. While direct empirical data are lacking at present, this article aims to stimulate investigation of NOS3 polymorphisms as potential modifiers in MPN pathophysiology.