INCREASED FREQUENCY OF SOMATIC MUTATIONS AT GLYCOPHORIN-A LOCI IN PATIENTS WITH APLASTIC-ANEMIA, MYELODYSPLASTIC SYNDROME AND PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA

Citation
H. Hattori et al., INCREASED FREQUENCY OF SOMATIC MUTATIONS AT GLYCOPHORIN-A LOCI IN PATIENTS WITH APLASTIC-ANEMIA, MYELODYSPLASTIC SYNDROME AND PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA, British Journal of Haematology, 98(2), 1997, pp. 384-391
Citations number
31
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Hematology
ISSN journal
0007-1048
Volume
98
Issue
2
Year of publication
1997
Pages
384 - 391
Database
ISI
SICI code
0007-1048(1997)98:2<384:IFOSMA>2.0.ZU;2-5
Abstract
Paroxysmal nocturnal haemoglobinuria (PNH), aplastic anaemia (AA) and myelodysplastic syndrome (MDS) are haemopoietic stem cell disorders. T hese disorders have some features in common, and a percentage of cases progress to acute leukaemia. We speculated that changes in gene stabi lity are involved in the pathogenesis of these haemopoietic stem cell disorders. Therefore we investigated in vivo mutation frequencies in t hese disorders by erythrocyte glycophorin A (GPA) mutation assay. The assay enumerates NO or NN variant cells in 10(6) erythrocytes of the M N type using a flowcytometric technique. Patients undergoing chemother apy known to be at risk of hypermutageneity were also studied. Events exceeding the 95th percentile of healthy donors (greater than or equal to 32 and 34 events, respectively for NO and NN variants) were define d as abnormal. Abnormal events in the NO variants were found in three out of seven patients undergoing chemotherapy, two out of nine patient s with AA, two out of seven patients with MDS, and four out of nine pa tients with PNH. Abnormal events in the NN variants were found in thre e out of seven patients undergoing chemotherapy, two out of nine patie nts with AA, one out of seven patients with MDS, and two out of nine p atients with PNH. These results suggest that not only PIG-A, but also other genes including the GPA gene, are hypermutable in haemopoietic s tem cell disorders, and that mutagenic pressure and/or gene instabilit y can contribute to the pathogenesis of these disorders.