ROLE OF TNF Α PROMOTER POLYMORPHISM G308A IN CHRONIC MYELOPROLIFERATIVE NEOPLASMS: MOLECULAR MECHANISMS, CLINICAL IMPLICATIONS, AND FUTURE PERSPECTIVES

Abstract

Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by excessive proliferation of one or more myeloid lineages. Inflammation and cytokine dysregulation are increasingly recognized as key contributors to disease initiation, progression, and phenotypic heterogeneity in MPNs. Tumor necrosis factor‑alpha (TNF‑α) is a central proinflammatory cytokine whose expression is regulated at the transcriptional level, in part via promoter polymorphisms such as the G→A substitution at position –308 (commonly called G308A, or rs1800629). The G308A polymorphism has been investigated in various inflammatory, oncologic, and hematologic disorders, but its specific role in MPNs remains underexplored. In this review, we summarize current knowledge of TNF‑α function in hematopoiesis and MPN pathophysiology, examine available evidence regarding the G308A polymorphism in hematologic and neoplastic diseases, propose mechanistic models for how the G308A variant might influence MPN phenotypes, and outline experimental and clinical strategies to test its relevance. We conclude that although direct data are scarce, the G308A polymorphism represents a plausible modulatory factor in MPNs, with potential value as a biomarker or therapeutic target, warranting deeper investigation.