Differential effect of type I interferons on hematopoietic progenitor cells: failure of interferons to inhibit IL-3-stimulated normal and CML myeloid progenitors.
We observed a differential effect of type I interferons (IFNs) in inhibiting the proliferation of various hematopoietic progenitor cell types. Upon stimulation with interleukin-3 (IL-3), IFN-alpha and IFN-beta failed to inhibit colony formation of myeloid progenitors (day-14 colony-forming units-granulocyte/macrophage [CFU-GM]) obtained from peripheral blood (PB) and bone marrow (BM) of untreated chronic myelogenous leukemia (CML) patients in chronic phase even at IFN doses as high as 10,000 U/mL. In contrast, day-7 CFU-GM stimulated with granulocyte colony-stimulating factor (G-CSF) and burst-forming units-erythroid (BFU-E) were readily inhibited by moderate doses of IFNs. IFN-resistant myeloid progenitor cells were also detected in normal BM but not in normal PB cells. When suboptimal doses of IL-3 were used in clonal progenitor cell assays, day-14 CFU-GM were not protected from the inhibitory action of IFN. The failure of IFN to inhibit immature myeloid progenitors was confirmed in normal and CML cells highly enriched in CD34-expressing cells. Combinations of growth factors were required for sufficient colony formation in these cells, whereas IL-3 alone provided only an inadequate stimulation, which was further inhibited by IFN. In purified CD34+ cells, day-14 CFU-GM were protected from IFN-mediated inhibition only upon stimulation with stem cell factor (SCF) in combination with IL-3 or G-CSF.
Department of Medicine, Johannes-Gutenberg-University, Mainz, Germany.
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D
Després
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J
Goldschmitt
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WE
Aulitzky
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C
Huber
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C
Peschel
D018952:Antigens, CD34 / Q000032:analysis; D001853:Bone Marrow / Q000473:pathology; D002455:Cell Division; D003114:Colony-Forming Units Assay; D015672:Erythroid Precursor Cells / Q000473:pathology; D006098:Granulocytes / Q000473:pathology*; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D007377:Interleukin-3 / Q000494:pharmacology*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology*; D008264:Macrophages / Q000473:pathology
D018952:Antigens, CD34; D007370:Interferon Type I; D007377:Interleukin-3