TNF and myelodysplastic syndrome: In LR-MDS or early MDS patients, apoptosis signaling is associated with multiple mechanisms: (1) activation of Fas signaling as a result of an increased level of pro-apoptotic cytokines (e.g., TGF-β, IFN-γ and TNF-α); (2) elevation of T-helper (Th) type 17; (3) dysfunctional B-cells; and (4) cytopenic regulatory T-cells (Treg) [139].