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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
1997-3-17
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pubmed:abstractText |
Paroxysmal nocturnal hemoglobinuria (PNH) results from somatic mutations in the PIG-A gene, leading to poor presentation of glycosylphosphatidylinositol (GPI)-anchored surface proteins. PNH frequently occurs in association with suppressed hematopoiesis, including frank aplastic anemia (AA). The relationship between GPI-anchored protein expression and bone marrow (BM) failure is unknown. To assess the hematopoietic defect in PNH, the numbers of CD34+ cells, committed progenitors (primary colony-forming cells [CFCs]), and long-term culture-initiating cells (LTC-ICs; a stem cell surrogate) were measured in BM and peripheral blood (PB) of patients with PNH/AA syndrome or patients with predominantly hemolytic PNH. LTC-IC numbers were extrapolated from secondary CFC numbers after 5 weeks of culture, and clonogenicity of LTC-ICs was determined by limiting dilution assays. When compared with normal volunteers (n = 13), PNH patients (n = 14) showed a 4.7-fold decrease in CD34+ cells and an 8.2-fold decrease in CFCs. LTC-ICs in BM and in PB were decreased 7.3-fold and 50-fold, respectively. Purified CD34+ cells from PNH patients had markedly lower clonogenicity in both primary colony cultures and in the LTC-IC assays. As expected, GPI-anchored proteins were decreased on PB cells of PNH patients. On average, 23% of monocytes were deficient in CD14, and 47% of granulocytes and 58% of platelets lacked CD16 and CD55, respectively. In PNH BM, 27% of CD34+ cells showed abnormal GPI-anchored protein expression when assessed by CD59 expression. To directly measure the colony-forming ability of GPI-anchored protein-deficient CD34+ cells, we separated CD34+ cells from PNH patients for the GPI+ and GPI-phenotype; CD59 expression was chosen as a marker of the PNH phenotype based on high and homogeneous expression on fluorescent staining. CD34+ CD59+ and CD34+ CD59-cells from PNH/AA patients showed similarly impaired primary and secondary clonogeneic efficiency. The progeny derived from CD34+ CD59- cells were both CD59- and CD55-. A very small population of CD34+ CD59- cells was also detected in some normal volunteers; after sorting, these CD34+ CD59- cells formed normal numbers of colonies, but their progeny showed lower CD59 levels. Our results are consistent with the existence of PIG-A-deficient clones in some normal individuals. In PNH/AA, progenitor and stem cells are decreased in number and function, but the proliferation in vitro is affected similarly in GPI-protein-deficient clones and in phenotypically normal cells. As measured in the in vitro assays, expansion of PIG-A- clones appears not be caused by an intrinsic growth advantage of cells with the PNH phenotype.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD34,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD59,
http://linkedlifedata.com/resource/pubmed/chemical/Glycosylphosphatidylinositols,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/phosphatidylinositol glycan-class...
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0006-4971
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
89
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1173-81
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pubmed:dateRevised |
2004-11-17
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pubmed:meshHeading |
pubmed-meshheading:9028939-Adolescent,
pubmed-meshheading:9028939-Adult,
pubmed-meshheading:9028939-Anemia, Aplastic,
pubmed-meshheading:9028939-Antigens, CD34,
pubmed-meshheading:9028939-Antigens, CD59,
pubmed-meshheading:9028939-Bone Marrow,
pubmed-meshheading:9028939-Cell Count,
pubmed-meshheading:9028939-Cell Division,
pubmed-meshheading:9028939-Cells, Cultured,
pubmed-meshheading:9028939-Clone Cells,
pubmed-meshheading:9028939-Female,
pubmed-meshheading:9028939-Glycosylphosphatidylinositols,
pubmed-meshheading:9028939-Hematopoiesis,
pubmed-meshheading:9028939-Hemoglobinuria, Paroxysmal,
pubmed-meshheading:9028939-Humans,
pubmed-meshheading:9028939-Male,
pubmed-meshheading:9028939-Membrane Proteins,
pubmed-meshheading:9028939-Middle Aged,
pubmed-meshheading:9028939-Myelodysplastic Syndromes
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pubmed:year |
1997
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pubmed:articleTitle |
Impaired hematopoiesis in paroxysmal nocturnal hemoglobinuria/aplastic anemia is not associated with a selective proliferative defect in the glycosylphosphatidylinositol-anchored protein-deficient clone.
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pubmed:affiliation |
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
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pubmed:publicationType |
Journal Article
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