1. Immune pathogenesis of apoptosis of CD34 multipotential hematopoietic cells in acquired aplastic anemia. Antigens are presented to T lymphocytes by antigen-presenting cells (APCs). This triggers T cells to activate and proliferate. T-bet, a transcription factor, binds to the interferon-γ (IFN-γ) promoter region and induces gene expression. SLAM-associated protein (SAP) binds to Fyn and modulates the signaling lymphocyte activation molecule (SLAM) activity on IFN-γ expression, diminishing gene transcription. Patients with aplastic anemia show constitutive T-bet expression and low SAP levels. IFN-γ and tumor necrosis factor-α (TNF-α) upregulate both the T cell's cellular receptors and the Fas receptor. Increased production of interleukin-2 leads to polyclonal expansion of T cells. Activation of the Fas receptor by the Fas ligand leads to apoptosis of target cells. Some effects of IFN-γ are mediated through interferon regulatory factor 1 (IRF-1), which inhibits the transcription of cellular genes and entry into the cell cycle. IFN-γ is a potent inducer of many cellular genes, including inducible nitric oxide synthase (NOS), and production of the toxic gas, nitric oxide (NO), may further diffuse the toxic effects. These events ultimately lead to reduced cell cycling and cell death by apoptosis. (Reproduced with permission from Young NS, Calado RT, Scheinberg P: Current concepts in the pathophysiology and treatment of aplastic anemia. Blood 2006 Oct 15;108(8): )
Source: Aplastic Anemia: Acquired and Inherited, Williams Hematology, 9e
Citation: Kaushansky K, Lichtman MA, Prchal JT, Levi MM, Press OW, Burns LJ, Caligiuri M. Williams Hematology, 9e; 2015 Available at: Accessed: October 10, 2017
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