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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
Source: Aplastic Anemia: Acquired and Inherited, Williams Hematology, 9e
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
Kaushansky
K, Lichtman
MA, Prchal
JT,(NOS),
Levi MM,
OW, Burns
Caligiuri
M. Williams
Hematology,
9e;diffuse
2015 Available
at:
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http://mhmedical.com/
Accessed:
May
07,
2017
These events ultimately lead to reduced cell cycling and cell death by apoptosis. (Reproduced with permission from Young NS, Calado RT, Scheinberg P:
Copyright
2017 McGraw-Hill
rights reserved
Current concepts
in the©pathophysiology
andEducation.
treatment All
of aplastic
anemia. Blood 2006 Oct 15;108(8):2509-2519.)