title: The hematopoietic defect in PNH is not due to defective stroma, but is due to defective progenitor cells.
abstract: Although paroxysmal nocturnal hemoglobinuria (PNH) is often associated with aplastic anemia (AA), the nature of the pathogenetic link between PNH and AA remains unclear. Moreover, the PIG-A mutation appears to be necessary but not sufficient for the development of PNH, suggesting other factors are involved. The ability of PNH marrow cells to form in vitro hematopoietic colonies and the ability of PNH marrow to generate stroma that could support hematopoiesis of normal or PNH marrow in cross culture were investigated. PNH marrow from both post-Ficoll and post-lineage depleted hematopoietic progenitor cells grew similarly significantly fewer colonies than normal marrow. Sorting of CD59(+) and CD59(-) CD34(+) CD38(-) cells from patients with PNH showed similarly impaired clonogenic efficiency, indicating that the hematopoietic defect in PNH does not directly relate to GPI-anchored protein expression. PNH marrow readily grew stroma similar to marrow from normal donors. Cross culture experiments revealed that PNH stroma appears to function normally in vitro; it can support growth of normal marrow cells as well as normal stroma does, but neither PNH nor normal stroma could support the growth of PNH marrow cells. The hematopoietic defect in PNH is not due to defective stroma, but is due to defective progenitor cell growth related to additional unknown factors.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Nishimura
authors.forename: Russell E
authors.initials: RE
authors.lastname: Ware
authors.forename: Angela
authors.initials: A
authors.lastname: Burnette
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Pendleton
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Kitano
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Hirota
authors.forename: Takashi
authors.initials: T
authors.lastname: Machii
authors.forename: Teruo
authors.initials: T
authors.lastname: Kitani
authors.forename: Clay A
authors.initials: CA
authors.lastname: Smith
authors.forename: Wendell F
authors.initials: WF
authors.lastname: Rosse
mesh_terms: D000328:Adult; D001854:Bone Marrow Cells / Q000473:pathology; D016022:Case-Control Studies; D002455:Cell Division; D018920:Coculture Techniques; D003114:Colony-Forming Units Assay; D004418:Dyspnea, Paroxysmal / Q000209:etiology / Q000473:pathology*; D005260:Female; D017261:Glycosylphosphatidylinositols; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D008297:Male; D017154:Stromal Cells / Q000166:cytology*
chemical_list: D017261:Glycosylphosphatidylinositols