title: Diamond-Blackfan anemia: promotion of marrow erythropoiesis in vitro by recombinant interleukin-3.
abstract: To clarify the defective erythropoiesis in eight patients with Diamond-Blackfan anemia, we studied their bone marrow response in vitro to recombinant human interleukin-3 (IL-3) and recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF). In an erythropoietin-containing assay system, specimens from six of the eight patients yielded low numbers of erythroid colonies compared to control values, and in five of these no erythropoietin dose-response could be elicited. Addition of IL-3, GM-CSF or both to cultures from the six patients had no effect on CFU-E-derived colonies. In contrast, IL-3 but not GM-CSF induced a marked increase in the number (183%) and size of the BFU-E-derived colonies in five of the six cases and partially corrected the impaired dose-response to erythropoietin in four. Bone marrow from the other two patients yielded numbers of CFU-E and BFU-E colonies comparable to controls and manifested similar increments in colonies with increasing concentrations of erythropoietin. When IL-3 was added to these cultures, further increments were observed in the number and size of BFU-E colonies. We conclude that IL-3 enhanced the marrow erythropoiesis in most of the patients and exerted a corrective effect on the aberrant colony formation in the presence of erythropoietin. The data raise the possibility of IL-3 as a therapeutic agent in Diamond-Blackfan anemia.
authors.affiliation: Division of Hematology/Oncology, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: D S
authors.initials: DS
authors.lastname: Halperin
authors.forename: Z
authors.initials: Z
authors.lastname: Estrov
authors.forename: M H
authors.initials: MH
authors.lastname: Freedman
mesh_terms: D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000097:blood / Q000473:pathology*; D001853:Bone Marrow / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D004920:Erythropoiesis / Q000187:drug effects*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000473:pathology / Q000502:physiology; D006801:Humans; D007223:Infant; D007377:Interleukin-3 / Q000494:pharmacology*; D008297:Male; D011994:Recombinant Proteins / Q000494:pharmacology*
chemical_list: D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007377:Interleukin-3; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor