title: Evaluation of the haemopoietic reservoir in de novo haemolytic paroxysmal nocturnal haemoglobinuria.
abstract: Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired clonal disorder of the haemopoietic stem cell (HSC). The pathogenetic link with bone marrow failure is well recognized; however, the process of clonal expansion of the glycosylphosphatidylinositol (GPI)-deficient cells over normal haemopoiesis remains unclear. We have carried out detailed analysis of the stem cell population in 10 patients with de novo haemolytic PNH using the long-term culture-initiating cells (LTC-IC) assay in parallel with measurements of CD34+ cells and mature haemopoietic progenitors, granulocyte-macrophage colony-forming unit (CFU-GM) and CFU-erythroid [burst-forming units erythroid (BFU-E) + CFU granulocyte/erythroid/macrophage/megakaryocyte (GEMM)]. All patients had hypercellular bone marrows with erythroid hyperplasia, normal blood counts or mild peripheral blood cytopenias, increased reticulocyte counts and evidence of deficient GPI-anchored proteins. We found a significant reduction in the LTC-IC frequency in the CD34+ compartment of PNH patients (mean 2, range 1.3-3.0; n=6) compared with normal donors (mean 13, range 5.2-45.5; n=21) (P<0.0001). Furthermore, there was a significant reduction in the erythroid compartment [CFU-E/105 bone marrow mononuclear cells (BMMC) and CFU-E/105 CD34+ cells] of PNH patients, but no significant difference in the granulocyte-monocyte precursors (CFU-GM/105 BMMC or CFU-GM/105 CD34+ cells) compared with normal donors, suggesting that there is a defect in the early stem cell pool in PNH patients without clinical or haematological evidence of bone marrow failure.
authors: Department of Haematology, St George's Hospital Medical School, London, UK. Dupe.Elebute@stgeorges.nhs.uk
authors: Modupe O
authors: MO
authors: Elebute
authors: Sian
authors: S
authors: Rizzo
authors: Jennifer A
authors: JA
authors: Tooze
authors: Judith C W
authors: JC
authors: Marsh
authors: Edward C
authors: EC
authors: Gordon-Smith
authors: Frances M
authors: FM
authors: Gibson
mesh_terms: D000328:Adult; D018952:Antigens, CD34 / Q000032:analysis; D016022:Case-Control Studies; D002452:Cell Count; D002478:Cells, Cultured; D002999:Clone Cells; D003114:Colony-Forming Units Assay; D005260:Female; D017261:Glycosylphosphatidylinositols / Q000172:deficiency; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D006457:Hemoglobinuria, Paroxysmal / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018709:Statistics, Nonparametric
chemical_list: D018952:Antigens, CD34; D017261:Glycosylphosphatidylinositols