title: Phenotypes and phosphatidylinositol glycan-class A gene abnormalities during cell differentiation and maturation from precursor cells to mature granulocytes in patients with paroxysmal nocturnal hemoglobinuria.
abstract: To define the phosphatidylinositol glycan-class A (PIG-A) gene abnormality in precursor cells and the changes of expression of glycosylphosphatidylinositol-anchored protein and contribution of paroxysmal nocturnal hemoglobinuria (PNH) clones with PIG-A gene abnormalities among various cell lineages during differentiation and maturation, we investigated CD59 expression on bone marrow CD34(+) cells and peripheral granulocytes from 3 patients with PNH and the PIG-A gene abnormalities in the CD59(-), CD59(+/-), and CD59(+) populations by nucleotide sequence analyses. We also performed clonogeneic assays of CD34(+)CD59(+) and CD34(+)CD59(-) cells from 2 of the patients and examined the PIG-A gene abnormalities in the cultured cells. In case 1, the CD34(+) cells and granulocytes consisted of CD59(-) and CD59(+) populations and CD59(-), CD59(+/-), and CD59(+) populations, respectively. Sequence analyses indicated that mutation 1-2 was in the CD59(+/-) granulocyte population (20 of 20) and the CD34(+)CD59(-) population (2 of 38). In cases 2 and 3, the CD34(+) cells and granulocytes consisted of CD59(+) and CD59(-) cells. Sequence analyses in case 3 showed that mutation 3-2 was not in CD34(+)CD59(-) cells and was present in the CD59(-) granulocyte population. However, PIG-A gene analysis of cultured CD34(+)CD59(-) cells showed that they had the mutation. This analysis also revealed that there were some other mutations, which were not found in CD34(+)CD59(-) cells and CD59(-) or CD59(+/-) granulocytes in vivo, and that sometimes they were distributed specifically among different cell lineages. In conclusion, our findings suggest that PNH clones might contribute qualitatively and quantitatively differentially to specific blood cell lineages during differentiation and maturation of hematopoietic stem cells.
authors.affiliation: First Department of Internal Medicine, Fukushima Medical University, Fukushima, Japan.
authors.forename: Tatsuyuki
authors.initials: T
authors.lastname: Kai
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Shichishima
authors.forename: Hideyoshi
authors.initials: H
authors.lastname: Noji
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Okamoto
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Ikeda
authors.forename: Yukio
authors.initials: Y
authors.lastname: Maruyama
mesh_terms: D000368:Aged; D018952:Antigens, CD34 / Q000032:analysis; D018957:CD59 Antigens / Q000032:analysis; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D002999:Clone Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004252:DNA Mutational Analysis; D006098:Granulocytes / Q000473:pathology*; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006457:Hemoglobinuria, Paroxysmal / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype
chemical_list: D018952:Antigens, CD34; D018957:CD59 Antigens; D008565:Membrane Proteins; C080086:phosphatidylinositol glycan-class A protein