title: Detection of GPI-anchored protein-deficient cells in patients with aplastic anaemia and evidence for clonal expansion during the clinical course.
abstract: The incidence of patients with aplastic anaemia (AA) who show a deficiency of glycosylphosphatidylinositol (GPI)-anchored proteins on their peripheral blood (PB) or bone marrow (BM) cells is higher than that previously reported. We analysed the expression of CD55 or CD59 on PB and BM cells and those of colonies and bursts formed in cultures with marrow cells from AA patients. 4/21 (19%) AA cases later developed paroxysmal nocturnal haemoglobinuria (PNH). 7/17 (41. 2%) AA cases showed a subpopulation without GPI-anchored proteins. The defect characteristic for PNH was observed only on the colonies/bursts but not on the PB or BM cells in three cases. We found the affected colonies/bursts in cultures using thawed marrow cells which had been cryopreserved at the diagnosis of aplasia in one patient who developed PNH 3 years later. Two different mutations of the PIG-A gene were found in the colonies/bursts at the time of AA. The nucleotide sequences were identical between the colonies/bursts at the time of AA and those after the transition to PNH. However, one of the mutations was detected only at the haemopoietic progenitor level but not in PB granulocytes. There may be latent subclones with PNH abnormalities which could expand to the level of clinical detection, or which do not progress and remain indolent for a relatively long time, implying the different extents of clonal expansion among the affected progenitors.
authors.affiliation: Second Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kawaguchi
authors.forename: H
authors.initials: H
authors.lastname: Wada
authors.forename: A
authors.initials: A
authors.lastname: Mori
authors.forename: Y
authors.initials: Y
authors.lastname: Takemoto
authors.forename: E
authors.initials: E
authors.lastname: Kakishita
authors.forename: A
authors.initials: A
authors.lastname: Kanamaru
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000741:Anemia, Aplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000378:metabolism; D018958:CD55 Antigens / Q000378:metabolism; D018957:CD59 Antigens / Q000378:metabolism; D002452:Cell Count; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D017261:Glycosylphosphatidylinositols / Q000172:deficiency* / Q000235:genetics; D006098:Granulocytes / Q000378:metabolism; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics
chemical_list: D018958:CD55 Antigens; D018957:CD59 Antigens; D017261:Glycosylphosphatidylinositols; D008565:Membrane Proteins; C080086:phosphatidylinositol glycan-class A protein