title: Erythropoiesis in Diamond-Blackfan anemia and the role of interleukin 3 and steel factor.
abstract: Diamond-Blackfan anemia (DBA) is pleiotropic clinically and in vitro, and there is a strong suspicion that DBA is really a family of diseases that shares a common hematological phenotype. Although standard clonogenic assays of erythroid progenitors have been very informative about pathogenesis, they are not diagnostic of DBA, have no relationship to the clinical presentation and do not relate to the hemoglobin level or to the percentage of marrow erythroids at the time of study. Studies on progenitor-enriched marrow cells have furthered our understanding of DBA and have clearly shown marked differences among patients with respect to erythropoietin and "burst-promoting activity" responsiveness. In vitro addition of corticosteroids, interleukin 3 (IL-3) and/or Steel factor has produced a corrective effect on erythropoiesis in some DBA patients and has prompted clinical trials with IL-3 with variable results. It is clear that there is a disparity between the vitro data and clinical outcome, and therefore, the erythroid progenitor responsiveness to steroids and cytokines has limited predictive value clinically. Based on more than two decades of study, a model of DBA has evolved based on putative blocks at various stages along the erythropoietic differentiation pathway. These blocks likely represent a disorder of receptor-ligand interaction involving one or more growth-promoting cytokines.
authors.affiliation: Division of Hematology-Oncology, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: M H
authors.initials: MH
authors.lastname: Freedman
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D002469:Cell Separation; D003114:Colony-Forming Units Assay; D004357:Drug Synergism; D015672:Erythroid Precursor Cells / Q000187:drug effects*; D004920:Erythropoiesis / Q000187:drug effects; D004921:Erythropoietin / Q000494:pharmacology / Q000627:therapeutic use; D005199:Fanconi Anemia / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology / Q000627:therapeutic use; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D007377:Interleukin-3 / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use; D011994:Recombinant Proteins; D019089:Stem Cell Factor
chemical_list: D016298:Hematopoietic Cell Growth Factors; D007155:Immunologic Factors; D007377:Interleukin-3; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D004921:Erythropoietin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor