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)

Paroxysmal nocturnal haemoglobinuria is an acquired haemolytic anaemia that may develop into aplastic anaemia or myeloid leukaemia. It has recently been shown that paroxysmal nocturnal haemoglobinuria is due to a defective coupling of specific proteins to glycolipids on the cell surface of haematopoietic cells. One of these proteins is decay-accelerating factor (DAF), and the absence of DAF on the surfaces of blood cells leads to the haemolytic symptoms. The molecular biology of DAF and its relationship to paroxysmal nocturnal haemoglobinuria symptoms is described in this brief review. The molecular defect of paroxysmal nocturnal haemoglobinuria is illustrated in a case report.
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PMID:[Paroxysmal nocturnal hemoglobinuria, a cell surface molecular defect]. 170 Feb 42

The lack of glycosylphosphatidylinositol (GPI)-anchored membrane proteins such as decay-accelerating factor (DAF) and CD59 on blood cells has a diagnostic value in paroxysmal nocturnal hemoglobinuria (PNH). Because PNH often develops in patients with aplastic anemia (AA), we attempted to detect a PNH clone in the bone marrow (BM) of patients with AA and pancytopenia before affected cells were evident in the peripheral blood (PB). We used flow cytometry with monoclonal antibodies against DAF and CD59 for the detection of the clone. Affected cells were observed in the BM of 3 of 7 patients with AA and 1 of 3 patients with pancytopenia of unknown origin, but not in their PB. All 8 patients with apparent PNH had affected cells in their BM and PB. On the basis of the early appearance of the PNH clone in the BM, a prospective 4-month follow-up study of the PB cells was performed. The study showed the release of affected mature cells first in granulocytes, then in monocytes, and finally in lymphocytes. Ham's test was positive before affected erythrocytes were detected by flow cytometry. Our findings indicate that detection of the PNH clone in BM could be predictive of the development of PNH in patients with AA and pancytopenia.
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PMID:Paroxysmal nocturnal hemoglobinuria clone in bone marrow of patients with pancytopenia. 753 41

Using a flow cytometric analysis, CD55 (decay-accelerating factor), CD59 and CD58 have been measured on neutrophils from 12 aplastic anaemia (AA) patients who were long-term survivors after immunosuppressive therapy (IS), 17 healthy individuals, four patients with PNH, and six patients with other haematological disorders. The neutrophils from normal control patients and the six patients with other haematological disorders showed 98 +/- 2% (mean +/- SD) positive granulocytes for CD55. Corresponding values were low (12%, 26%, 51% and 58%) on the primarily PNH patients. Among the 12 AA patients examined, seven had normal and five low values (59% in two, 70%, 71% and 82%). Among the five AA patients who showed CD55 neutrophil deficiency, four had showed an incomplete response after the initial IS treatment and the other relapsed following an initial haematological complete response; three cases had a positive Ham's test and two were negative. Our data suggest that the development of PNH clones is a frequent finding in AA long-term survivors, mainly in those who had shown an incomplete response following IS. Neutrophil CD55 expression analysis by flow cytometry could be useful to detect clonal evolution in these patients.
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PMID:Flow cytometric analysis of decay-accelerating factor (CD55) on neutrophils from aplastic anaemia patients. 754 52

Using flow cytometry, decay-accelerating factor (DAF) and CD59 have been measured in peripheral blood cells of 11 patients with aplastic anaemia and 34 healthy controls. Ten of the patients had monophasic fluorescence profiles similar to those of the controls. However, one patient had small DAF- and CD59-negative populations in granulocytes and monocytes, but not in erythrocytes. One year after the first assay, a second flow cytometric study revealed that all peripheral blood cell species, including erythrocytes, contained DAF- and CD59-deficient populations. At this time, a sucrose haemolysis test was positive. This is the first reported case of aplastic anaemia-PNH syndrome in which DAF- and CD59-negative cells appeared first in granulocytes and monocytes and later in all types of peripheral blood cells.
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PMID:Decay-accelerating factor and CD59 expression in peripheral blood cells in aplastic anaemia and report of a case of paroxysmal nocturnal haemoglobinuria secondary to aplastic anaemia. 768 37

The purpose of this review is to summarize recent studies that have led to a more complete understanding of the molecular basis of paroxysmal nocturnal hemoglobinuria (PNH). Somatic mutations of PIG-A arising in pluripotent hematopoietic stem cells are necessary for the development of PNH. PIG-A is an X-linked gene that is essential for synthesis of the glycosyl phosphatidylinositol (GPI) moiety that serves as a membrane anchor for a functionally diverse group of cell surface proteins. Consequently, the progeny of stem cells with mutant PIG-A are deficient in all GPI-anchored proteins (GPI-AP). Among the GPI-AP that are expressed on hematopoietic cells are two important regulators of the complement system, decay-accelerating factor, (CD55) and membrane inhibitor of reactive lysis, (CD59). It is the deficiency of erythrocyte CD55 and CD59 that accounts for the intravascular hemolysis and hemoglobinuria that are the clinical hallmarks of PNH. A remarkable feature of PNH is that the peripheral blood is a mosaic composed of variable proportions of GPI-AP+ and GPI-AP- cells and that, in an individual patient, the GPI-AP- cells can be derived from multiple mutant stem cells. Currently, however, there is no evidence that the PIG-A mutation per se provides a proliferative advantage. Thus, PNH is not a monoclonal disease with a malignant phenotype. Rather, the mutant stem cells appear to dominate hematopoiesis because under some pathological conditions, GPI-AP deficiency is advantageous. The close association of PNH with aplastic anemia suggests that the selection pressure arises as a consequence of a specific type of bone marrow injury.
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PMID:Molecular basis of paroxysmal nocturnal hemoglobinuria. 884 41

Among acquired stem cell disorders, pathological links between myelodysplastic syndromes (MDS) and aplastic anaemia (AA), and paroxysmal nocturnal haemoglobinuria (PNH) and AA, have been often described, whereas the relationship between MDS and PNH is still unclear. We analysed blood cells of patients with MDS to determine the incidence of the PNH clone, and analysed the PIG-A gene to find mutations characteristic of the PNH clone in MDS. In four (10%) of 40 patients with MDS, flow cytometry showed affected erythrocytes and granulocytes negative for decay-accelerating factor (DAF) and CD59. The population of affected erythrocytes was smaller in MDS patients with PNH clone (MDS/PNH) than in patients with de novo PNH, and haemolysis was milder in the MDS/PNH patients. PIG-A mutations were found in granulocytes of all patients with MDS/PNH. In type and site, the PIG-A mutations were heterogeneous, similar to that observed in de novo PNH; i.e. no mutation specific to MDS/PNH was identified. Of note, three of four patients with MDS/PNH each had two PNH clones with different PIG-A mutations, suggesting that PIG-A is mutable in patients with MDS/PNH. In a MDS/PNH patient with trisomy 8, FISH detected a distinct karyotype in a portion of granulocytes with PNH phenotype, indicating that PNH and MDS partly shared affected cells. Thus, MDS predisposes to PNH by creating conditions favourable to the genesis of PNH clone. Considering the increasing prevalence and incidence of MDS, these disorders could be useful for investigating the mechanism by which PIG-A mutation is induced.
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PMID:Paroxysmal nocturnal haemoglobinuria clones in patients with myelodysplastic syndromes. 1155 7