title: Origin and fate of blood cells deficient in glycosylphosphatidylinositol-anchored protein among patients with bone marrow failure.
abstract: Peripheral blood from 489 recently diagnosed patients with aplastic anaemia (AA) and 316 with refractory anaemia (RA) of myelodysplastic syndrome was evaluated to characterize CD55(-)CD59(-) [paroxysmal nocturnal haemoglobinuria (PNH)]-type blood cells associated with bone marrow (BM) failure. PNH-type cells were detected in 57% and 20% of patients with AA and RA, respectively. The percentages of PNH-type granulocytes ranged from 0.003% to 94.2% and the distribution was log-normal with a median of 0.178%. Serial analyses of 75 patients with PNH-type cells over 5 years revealed that the percentage of PNH-type cells constantly increased in 13 (17%), persisted in 44 (59%), disappeared in the remaining 18 (24%) although even in the 'Disappearance' group, PNH-type granulocytes persisted for at least 6 months. A scattergram profile of PNH-type cells unique to each patient persisted regardless of the response to immunosuppressive therapy and only single PIGA mutations were detected in PNH-type granulocytes sorted from four patients. These findings suggest that the PNH-type cells in patients with BM failure are derived from single PIGA mutant haematopoietic stem cells even when their percentages are <1% and their fate depends on the proliferation and self-maintenance properties of the individual PIGA mutants.
authors: Cellular Transplantation Biology, Division of Cancer Medicine, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan.
authors: Chiharu
authors: C
authors: Sugimori
authors: Kanako
authors: K
authors: Mochizuki
authors: Zhirong
authors: Z
authors: Qi
authors: Naomi
authors: N
authors: Sugimori
authors: Ken
authors: K
authors: Ishiyama
authors: Yukio
authors: Y
authors: Kondo
authors: Hirohito
authors: H
authors: Yamazaki
authors: Akiyoshi
authors: A
authors: Takami
authors: Hirokazu
authors: H
authors: Okumura
authors: Shinji
authors: S
authors: Nakao
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000741:Anemia, Aplastic / Q000097:blood / Q000235:genetics; D005500:Follow-Up Studies; D017261:Glycosylphosphatidylinositols / Q000097:blood / Q000172:deficiency*; D006098:Granulocytes / Q000378:metabolism; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood* / Q000235:genetics; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000235:genetics
chemical_list: D017261:Glycosylphosphatidylinositols; D008565:Membrane Proteins; C080086:phosphatidylinositol glycan-class A protein