title: Proliferative capacity of single isolated CD34+ hematopoietic stem/progenitor cells in paroxysmal nocturnal hemoglobinuria.
abstract: Paroxysmal nocturnal hemoglobinuria (PNH) results from somatic mutations of the X-linked PIG-A (phosphatidylinositol glycan-class A) gene, which occurs on a hematopoietic stem cell level, leading to a proportion of blood cells being deficient in all glycosylphosphatidylinositol (GPI)-anchored surface proteins. Although these GPI-deficient cells can explain many of the clinical symptoms of PNH, the pathogenesis of PNH is still somewhat obscure and many questions remain. To assess the hematopoietic defect involved in PNH, CD34+ CD59+ (normal phenotype hematopoietic stem/progenitor) and CD34+ CD59- (PNH phenotype) cells from PNH patients (n = 16) and CD34+ CD59+ cells from healthy volunteers (n = 10) were sorted as single cells into 96-well flat-bottom culture plates containing culture medium supplemented with stem cell factor, interleukin (IL)-3, erythropoietin, granulocyte-macrophage-colony-stimulating factor (GM-CSF), G-CSF, IL-6, thrombopoietin, and Flt-3 ligand. We found that the single PNH CD34+ CD59- cells had a growth advantage over the single CD34+ CD59+ cells to some extent, but they both had impaired growth abilities compared with CD34+ cells from healthy volunteers.
authors.affiliation: Department of Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People's Republic of China. hanbing1968@hotmail.com
authors.forename: B
authors.initials: B
authors.lastname: Han
authors.forename: Y
authors.initials: Y
authors.lastname: Wu
authors.forename: Z
authors.initials: Z
authors.lastname: Lu
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D018952:Antigens, CD34 / Q000032:analysis; D001853:Bone Marrow / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002469:Cell Separation; D002478:Cells, Cultured / Q000187:drug effects; D003114:Colony-Forming Units Assay; D004921:Erythropoietin / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D017261:Glycosylphosphatidylinositols / Q000172:deficiency / Q000502:physiology; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000473:pathology*; D006457:Hemoglobinuria, Paroxysmal / Q000473:pathology*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000494:pharmacology / Q000502:physiology; D008875:Middle Aged; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D018952:Antigens, CD34; D017261:Glycosylphosphatidylinositols; D016298:Hematopoietic Cell Growth Factors; D008565:Membrane Proteins; D011994:Recombinant Proteins; C084881:flt3 ligand protein; C080086:phosphatidylinositol glycan-class A protein; D004921:Erythropoietin