title: Preferential hematopoiesis by paroxysmal nocturnal hemoglobinuria clone engrafted in SCID mice.
abstract: In paroxysmal nocturnal hemoglobinuria (PNH), little is known about the molecular events leading to the clinical manifestations except for the hemolysis. To unfold the complex pathophysiology, it is necessary to elucidate the nature of the PNH clone. PNH exhibits an acquired stem cell disorder, a clonal expansion of affected cells, concomitant depression of normal hematopoiesis in bone marrow (BM), and, although infrequently, the development of leukemia. The PNH clone is thus expected to exhibit some neoplastic features. We report here that CD34+ hematopoietic progenitor cells of PNH-BM yielded blood cells of three lineages with PNH phenotype alone when transplanted into sublethally irradiated severe combined immunedeficient mice. The hematopoiesis persisted for more than 10 months and did not always need human cytokines. In contrast, the hematopoiesis by control grafts obtained from healthy volunteers required an intense cytokine treatment. This in vivo model defines the preferential hematopoiesis of pluripotent PNH progenitor cells, indicating the intrinsic growth abnormality of PNH clone.
authors.affiliation: Second Department of Internal Medicine, Kumamoto University School of Medicine, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Iwamoto
authors.forename: T
authors.initials: T
authors.lastname: Kawaguchi
authors.forename: K
authors.initials: K
authors.lastname: Horikawa
authors.forename: S
authors.initials: S
authors.lastname: Nagakura
authors.forename: T
authors.initials: T
authors.lastname: Kagimoto
authors.forename: T
authors.initials: T
authors.lastname: Suda
authors.forename: K
authors.initials: K
authors.lastname: Takatsuki
authors.forename: H
authors.initials: H
authors.lastname: Nakakuma
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D018952:Antigens, CD34; D001483:Base Sequence; D002999:Clone Cells / Q000637:transplantation; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D006085:Graft Survival; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006457:Hemoglobinuria, Paroxysmal / Q000473:pathology*; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011828:Radiation Chimera; D014183:Transplantation, Heterologous
chemical_list: D018952:Antigens, CD34; D017261:Glycosylphosphatidylinositols; D008565:Membrane Proteins; C080086:phosphatidylinositol glycan-class A protein