The mechanism of acquired aplastic anemia (AA), a bone marrow hematopoiesis failure disease, has not been fully understood. TNF-α is a pleiotropic cytokine involved in cell proliferation, differentiation and death, and inflammation through binding to specific receptors on cell membranes. Aberrant secretion of TNF-α contributes to a number of human diseases, including tumor development and inflammation. TNF-α is also an important negative regulator of hematopoiesis. Over-expression of TNF-α not only directly inhibits the proliferation and differentiation of hematopoietic cells, but also initiates the intracellular death pathway to induce hematopoietic cell death, leading to bone marrow hematopoiesis failure. In this review, we summarize the mechanisms underlying extrinsic apoptosis and necroptosis of hematopoietic cells induced by TNF-α, and discuss the role of TNF-α-induced programmed cell death in the pathogenesis of acquired AA.
Keywords: acquired aplastic anemia; caspase-dependent apoptosis; caspase-independent necroptosis; cytokines; tumor necrosis factor-α.