title: Expansion of donor-derived hematopoietic stem cells with PIGA mutation associated with late graft failure after allogeneic stem cell transplantation.
abstract: A small population of CD55(-)CD59(-) blood cells was detected in a patient who developed donor-type late graft failure after allogeneic stem cell transplantation (SCT) for treatment of aplastic anemia (AA). Chimerism and PIGA gene analyses showed the paroxysmal nocturnal hemoglobinuria (PNH)-type granulocytes to be of a donor-derived stem cell with a thymine insertion in PIGA exon 2. A sensitive mutation-specific polymerase chain reaction (PCR)-based analysis detected the mutation exclusively in DNA derived from the donor bone marrow (BM) cells. The patient responded to immunosuppressive therapy and achieved transfusion independence. The small population of PNH-type cells was undetectable in any of the 50 SCT recipients showing stable engraftment. The de novo development of donor cell-derived AA with a small population of PNH-type cells in this patient supports the concept that glycosyl phosphatidylinositol-anchored protein-deficient stem cells have a survival advantage in the setting of immune-mediated BM injury.
authors.affiliation: Cellular Transplantation Biology, Division of Cancer Medicine, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Mochizuki
authors.forename: Chiharu
authors.initials: C
authors.lastname: Sugimori
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Qi
authors.forename: Xuzhang
authors.initials: X
authors.lastname: Lu
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Takami
authors.forename: Ken
authors.initials: K
authors.lastname: Ishiyama
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kondo
authors.forename: Hirohito
authors.initials: H
authors.lastname: Yamazaki
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Okumura
authors.forename: Shinji
authors.initials: S
authors.lastname: Nakao
mesh_terms: D000741:Anemia, Aplastic / Q000235:genetics / Q000628:therapy; D006084:Graft Rejection / Q000209:etiology* / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006457:Hemoglobinuria, Paroxysmal / Q000235:genetics / Q000628:therapy; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D013997:Time Factors; D014019:Tissue Donors; D018183:Transplantation Chimera / Q000235:genetics; D014184:Transplantation, Homologous
chemical_list: D008565:Membrane Proteins; C080086:phosphatidylinositol glycan-class A protein