title: Effects of four species of interferon-alpha on cultured erythroid progenitors from congenital dyserythropoietic anaemia type I.
abstract: The in vitro effects of interferon (IFN)-alpha on erythroid progenitor cells derived from the peripheral blood of five patients with congenital dyserythropoietic anaemia (CDA) type I and seven healthy adults were studied. Ficol-hypaque-separated mononuclear cells were cultured for 14 d in StemGEM-1d medium with 0, 1, 10 and 100 U/ml of recombinant IFN-alpha2a, recombinant IFN-alpha2b, the genetically-engineered hybrid molecule IFN-alpha(1-8) or the laboratory-designed molecule IFN-alpha(consensus). Erythroid bursts and colonies were counted, picked and processed for electron microscopy. In the experiments employing IFN-alpha2a there were no differences in the numbers of erythroid bursts or colonies between four patients with CDA type I and seven healthy adults. All five patients with CDA type I showed the 'Swiss-cheese' ultrastructural abnormality of the heterochromatin in a proportion of the erythroblasts when the progenitor cells were cultured in the absence of added IFN-alpha. A statistically significant reduction in the proportion of erythroblasts showing the 'Swiss-cheese' defect was seen when the erythroid progenitors were cultured in the presence of 0.01-0.5 U/ml IFN-alpha2a (five patients), or 0.1 U/ml of IFN-alpha2b (two patients). In contrast, no reduction was seen in cultures containing 0.1-100 U/ml of either IFN-alpha(1-8) or IFN-alpha(consensus) or 20 microM hydroxyurea (two patients). The partial correction of the 'Swiss-cheese' abnormality by low concentrations of IFN-alpha2a in vitro provides an experimental model with which the mechanisms underlying the haematological response that occurs after the in vivo administration of this species of IFN-alpha may be investigated.
authors.affiliation: Department of Haematology, Imperial College School of Medicine, St Mary's Campus, London.
authors.forename: D
authors.initials: D
authors.lastname: Menike
authors.forename: S N
authors.initials: SN
authors.lastname: Wickramasinghe
mesh_terms: D000328:Adult; D000742:Anemia, Dyserythropoietic, Congenital / Q000097:blood*; D002478:Cells, Cultured; D004900:Erythroblasts / Q000648:ultrastructure; D015672:Erythroid Precursor Cells / Q000473:pathology*; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D011994:Recombinant Proteins
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins