Document Detail


Increased frequency of somatic mutations at glycophorin A loci in patients with aplastic anaemia, myelodysplastic syndrome and paroxysmal nocturnal haemoglobinuria.
MedLine Citation:
PMID:  9266937     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Paroxysmal nocturnal haemoglobinuria (PNH), aplastic anaemia (AA) and myelodysplastic syndrome (MDS) are haemopoietic stem cell disorders. These disorders have some features in common, and a percentage of cases progress to acute leukaemia. We speculated that changes in gene stability are involved in the pathogenesis of these haemopoietic stem cell disorders. Therefore we investigated in vivo mutation frequencies in these disorders by erythrocyte glycophorin A (GPA) mutation assay. The assay enumerates NO or NN variant cells in 106 erythrocytes of the MN type using a flowcytometric technique. Patients undergoing chemotherapy known to be at risk of hypermutageneity were also studied. Events exceeding the 95th percentile of healthy donors (> or = 32 and 34 events, respectively for NO and NN variants) were defined as abnormal. Abnormal events in the NO variants were found in three out of seven patients undergoing chemotherapy, two out of nine patients with AA, two out of seven patients with MDS, and four out of nine patients with PNH. Abnormal events in the NN variants were found in three out of seven patients undergoing chemotherapy, two out of nine patients with AA, one out of seven patients with MDS, and two out of nine patients with PNH. These results suggest that not only PIG-A, but also other genes including the GPA gene, are hypermutable in haemopoietic stem cell disorders, and that mutagenic pressure and/or gene instability can contribute to the pathogenesis of these disorders.
Authors:
H Hattori; T Machii; E Ueda; M Shibano; T Kageyama; T Kitani
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  British journal of haematology     Volume:  98     ISSN:  0007-1048     ISO Abbreviation:  Br. J. Haematol.     Publication Date:  1997 Aug 
Date Detail:
Created Date:  1997-09-18     Completed Date:  1997-09-18     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  0372544     Medline TA:  Br J Haematol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  384-91     Citation Subset:  IM    
Affiliation:
Department of Haematology and Oncology, Osaka University Medical School, Japan.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Anemia, Aplastic / genetics*
Gene Frequency
Glycophorin / genetics*
Hemoglobinuria, Paroxysmal / genetics*
Humans
Middle Aged
Mutation*
Myelodysplastic Syndromes / genetics*
Chemical
Reg. No./Substance:
0/Glycophorin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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