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)

Bone marrow and peripheral blood cells may be adversely affected by drugs. Although the risk from most drugs is very small, many cases are reported because of the millions of doses of drugs taken each year by the population. Neutropenia, thrombocytopenia, hemolytic anemia, aplastic anemia, and macrocytic anemia are the commonest effects, in that order. Aplastic anemia is rare, but very serious when it does occur. Adverse effects may be produced by a direct toxic action of the drug or its metabolites on the bone marrow or, less often, on circulating cells. Antineoplastic drugs and chloramphenicol are examples. Most drugs produce their adverse effects through an immunological mechanism. The drug may act as a hapten or may affect the immune system leading to the production of antidrug antibodies and sometimes autoantibodies. Hemolytic anemia may result. Penicillins may behave in this manner. Some drugs act on erythrocytes with enzyme defects, e.g. glucose-6-phosphate dehydrogenase (G-6-PD) abnormalities, to produce hemolysis. In many cases, the mechanism underlying the adverse effect is unknown. The paper lists the drugs reported to have caused some hematological adverse effect and describes the mechanisms in those cases where they are known.
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PMID:Hematologic side effects of drugs. 266 27

The kinetics of hematopoietic stem cells were investigated in glucose-6-phosphate dehydrogenase (G-6-PD) heterozygous cats treated with dimethylbusulfan. Because of X-chromosome inactivation during embryogenesis, each somatic cell from these animals contains either maternal- or paternal-type G-6-PD. Therefore, all hematopoietic progenitor cells carry the G-6-PD phenotype of the most primitive cell (stem cell) from which they originate. For up to 6.5 years after dimethylbusulfan therapy, we determined the percentages of erythroid and granulocyte/macrophage progenitor cells with each G-6-PD phenotype. Significant variations were seen in studies from five of six cats, showing that the population of stem cells contributing to hematopoiesis was neither large nor constant. With mathematical analyses, we estimated that the proliferative potential of residual stem cells was much less than that of normal stem cells reduced in number by autologous transplantation (Abkowitz et al, Proc Natl Acad Sci USA 87:9062, 1990). There was no evidence for the regeneration of a normal stem cell reserve over time; rather, damage was most pronounced years after dimethylbusulfan exposure. These data may help explain the high clinical incidence of aplastic anemia and myelodysplasia after alkylating agent therapies.
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PMID:Behavior of feline hematopoietic stem cells years after busulfan exposure. 840 Feb 59

Severe aplastic anemia (SAA) is a syndrome of severe bone marrow failure with high mortality. Our previous studies have demonstrated that both immature and activated DC1 increased in the bone marrow of SAA patients, and the balance of DC1 subsets shifted the stable form to active one, which might promote Th0 cells to polarize to Th1 cells and cause the over-function of T lymphocytes and hematopoiesis failure in SAA. So we assumed myeloid dendritic cells (mDCs) may be the key immune cells that cause destruction of hematopoietic cells in SAA, but the mechanism of activation of mDCs is unclear. Here, we investigated the proteome of mDCs in SAA patients to further explore the pathogenesis of SAA and the possible antigen that leads to immune activation in SAA. mDCs from 12 SAA patients, 12 remission patients and 12 controls were sorted by flow cytometry and examined by two-dimensional gel electrophoresis and mass spectrometry. Intensity changes of 41 spots were detected with statistical significance. Nine of the 41 spots were identified by MALDI-TOF/TOF tandem mass spectrometry. Changes in protein expression levels were found in the SAA group. These changes reveal that abnormal expression of cofilin, glucose-6-phosphate dehydrogenase and pyruvate kinase enzyme M2 in mDCs from SAA patients may be the reason for mDC hyperfunction.
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PMID:Differential expression of the proteome of myeloid dendritic cells in severe aplastic anemia. 2418 80