An interferon resistant variant of the hairy-cell leukemic cell line, Eskol: biochemical and immunological characterization.
The B-lymphoblastoid cell line Eskol, which is composed of differentiated cells resembling hairy-cell leukemia, has been used to study the effects of type I interferon in vitro. In order to study the mechanism of delayed interferon therapy resistance, a hairy-cell leukemia-like clonal cell line (IREs-4) was isolated from Eskol after 4 months of exposure to r-metIFN-con1. When compared to Eskol cells, the IREs-4 cells were resistant to the antiproliferative effect of type I interferons as well as interferon induced protection against LAK cells. Treatment of IREs-4 with type I interferon did not induce MHC antigens, although both MHC class I and II antigens were induced in Eskol. Binding studies indicated the presence of equal numbers of high affinity binding sites with similar affinities on both cell lines. The resistant phenotype appears to result from an intracellular event which is essential to interferon signal transduction. It is hypothesized that this variant may reflect heterogeneity in the normal population of hairy-cell leukemia cells, and may explain the partial resistance of HCL patients to IFN therapy.
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Department of Biology, Indiana University, Bloomington 47405.
Klein
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Reiter
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Taylor
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D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D003601:Cytotoxicity Tests, Immunologic; D004351:Drug Resistance; D014644:Genetic Variation; D006684:HLA-DR Antigens / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D007943:Leukemia, Hairy Cell / Q000276:immunology* / Q000378:metabolism; D012313:RNA / Q000032:analysis; D017471:Receptors, Interferon / Q000378:metabolism; D014407:Tumor Cells, Cultured
D006684:HLA-DR Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007370:Interferon Type I; D017471:Receptors, Interferon; D012313:RNA