title: Diamond Blackfan anaemia: differential pattern of in vitro progenitor response to macrophage inflammatory protein 1-alpha.
abstract: The congenital disorder of erythropoiesis Diamond Blackfan anaemia (DBA) exhibits a defect in the stem/progenitor cell compartment, located at the erythroid progenitor level (CFU-GEMM, BFU-E, CFU-E). Treatment of DBA with interleukin-3 (IL-3) has had limited effect, despite in vitro studies suggesting that progenitor cells were capable of responding to IL-3. Whether IL-3 is not reaching the appropriate defective target cell, the cells cannot respond, or the marrow humoral inhibitory system is overriding it, is not clear. To investigate humoral inhibitory activities we examined the response of 15 DBA bone marrows in vitro to the inhibitory chemokine macrophage inflammatory protein 1-alpha (MIP1-alpha) in the presence of the stimulatory cytokines erythropoietin, granulocyte-macrophage colony-stimulating factor, IL-3, and stem cell factor. In vitro data agreed with our previous work showing that our patients formed three statistically different groups in response to stimulatory cytokines (type I DBA erythroid colony numbers approximately normal > type II DBA > type III DBA). Addition of MIP1-alpha to cultures caused average erythroid and myeloid suppression, which sequentially increased with DBA type (type I inhibition < type II < type III). The differential level of inhibition shown by MIP1-alpha in these DBA patients lends further evidence for the presence of distinct subgroups in this disorder.
authors.affiliation: Division of Haematology, St George's Medical School, London.
authors.forename: C P
authors.initials: CP
authors.lastname: McGuckin
authors.forename: W M
authors.initials: WM
authors.lastname: Liu
authors.forename: S E
authors.initials: SE
authors.lastname: Ball
authors.forename: E C
authors.initials: EC
authors.lastname: Gordon-Smith
authors.forename: M R
authors.initials: MR
authors.lastname: Uhr
mesh_terms: D000293:Adolescent; D000328:Adult; D000917:Antibody Formation; D002455:Cell Division / Q000187:drug effects; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D002648:Child; D002675:Child, Preschool; D003114:Colony-Forming Units Assay; D015672:Erythroid Precursor Cells / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D004921:Erythropoietin / Q000494:pharmacology; D005199:Fanconi Anemia / Q000097:blood / Q000145:classification / Q000276:immunology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D006801:Humans; D007223:Infant; D007377:Interleukin-3 / Q000494:pharmacology; D019402:Macrophage Inflammatory Proteins; D008297:Male; D015846:Monokines / Q000494:pharmacology*; D019089:Stem Cell Factor / Q000494:pharmacology
chemical_list: D054405:Chemokine CCL3; D054407:Chemokine CCL4; D007377:Interleukin-3; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D019089:Stem Cell Factor; D004921:Erythropoietin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor