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Review
All Roads Lead to Interferon-γ: From Known to Untraveled Pathways in Acquired Aplastic Anemia.
- Bianca Serio, Valentina Giudice, and Carmine Selleri.
- Department of Medicine, Surgery, and Dentistry "Scuola Medica Salernitana", University of Salerno, 84081 Baronissi, Italy.
- Medicina (Kaunas). 2023 Dec 14; 59 (12).
AbstractBone marrow failure (BMF) syndromes are a heterogeneous group of benign hematological conditions with common clinical features including reduced bone marrow cellularity and peripheral blood cytopenias. Acquired aplastic anemia (AA) is caused by T helper(Th)1-mediated immune responses and cytotoxic CD8+ T cell-mediated autologous immune attacks against hematopoietic stem and progenitor cells (HSPCs). Interferon-γ (IFNγ), tumor necrosis factor-α, and Fas-ligand are historically linked to AA pathogenesis because they drive Th1 and cytotoxic T cell-mediated responses and can directly induce HSPC apoptosis and differentiation block. The use of omics technologies has amplified the amount of data at the single-cell level, and knowledge on AA, and new scenarios, have been opened on "old" point of view. In this review, we summarize the current state-of-art of the pathogenic role of IFNγ in AA from initial findings to novel evidence, such as the involvement of the HIF-1α pathway, and how this knowledge can be translated in clinical practice.
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