Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002874 (aplastic anemia)
 5,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increased expression of Fas by hematopoietic progenitors in aplastic anemia (AA) suggests that Fas/Fas ligand (FasL) system plays a key role in the formation of severe pancytopenia. To further confirm the above hypothesis, T cells from 8 patients with AA were systematically studied for their FasL's distribution pattern, releasing manner and proapoptotic activity, compared with normal resting T cells and artificially activated T cell blasts. The results demonstrated that AA T cells abnormally expressed low levels of membrane-bound FasL and contained high levels of intracellular FasL which could be triggered to release by high-dose phytohemagglutinin (PHA) pulse-stimulation. The supernatants from the PHA-stimulated AA T cells had apparent cytotoxicity against FasL-sensitive Jurkat cells, which could be significantly inhibited by monoclonal antibody against FasL in a dose-dependent manner, or nearly completely abrogated by ultracentrifugation. The above phenomena also appeared on artificially activated T cell blasts, but this was not the case on normal resting T cells. These results indicate that AA T cell is a type of "preactivated" T lymphocyte, characterized by overexpression of FasL, especially intracellular FasL which can be stimulated to release in bioactive exosomes-bound form. Taken together, our data provide further and direct evidence for the hypothesis that T cells might mediate the destruction of hematopoietic progenitor in AA through Fas/FasL system.
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PMID:Distinct overexpression of Fas ligand on T lymphocytes in aplastic anemia. 1621 2

Chloramphenicol is a broad-spectrum antibiotic used for the treatment of many infectious diseases and has become one of the major seafood contaminants. Hematologic disorders such as aplastic anemia and leukemia induced by chloramphenicol are a major concern. However, the mechanism underlying chloramphenicol-induced leukemogenesis is not known. By investigating the effects of chloramphenicol on the activation of mouse T cells stimulated with anti-CD3 antibody or staphylococcal enterotoxin B, we found that chloramphenicol induces the differentiation of activated T cells into lymphoblastic leukemia-like cells, characterized by large cell size, multiploid nuclei, and expression of CD7, a maker for immature T cells and T-cell lymphocytic leukemia, thus phenotypically indicating differentiation toward leukemogenesis. High expression of cyclin B1, but not p53, c-myc, and CDC25A, was detected in chloramphenicol-treated activated T cells, which may relate to abnormal cell differentiation. Chloramphenicol inhibited the activation-induced cell death of mouse and human T-cell receptor-activated T cells by down-regulating the expression of Fas ligand. Our findings show that abnormal cell differentiation and inhibition of apoptosis may contribute to the development of leukemia associated with clinical applications of chloramphenicol.
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PMID:Chloramphenicol induces abnormal differentiation and inhibits apoptosis in activated T cells. 1855 35


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