Homozygous and hemizygous deletions of the interferon A (IFNA) and IFNB genes have been frequently observed in acute leukemia cell lines, primary acute leukemia cases, and gliomas. Because IFNs have an antiproliferative effect, selection against the IFNα/β system could play a role or accompany the development of the malignant phenotype. Although the deletion of the IFNA/B genes could interrupt an autocrine loop that controls cell proliferation, cells would still respond to exogenous IFNα/β and, thus, lesions at the receptor or signal transduction level should also be present to render cells resistant to exogenous IFNα/β. To test if selection against the IFN system was operating in acute leukemias, the sensitivity to the antiproliferative effect of IFNα2 was studied in acute leukemia cell lines with and without alterations of the IFNA/B genes. We found that 10 of 11 acute leukemia cell lines with alterations of the IFNA/B genes were resistant to the antiproliferative effect of IFNα2, whereas only two of eight cell lines with normal IFNA/B genes were IFN-resistant. We then examined the possibility that an alteration of the receptor expression could account for the lack of response to IFNα2. No significant alteration in the expression or structure of the IFNα receptor was observed. We also studied the downmodulation of the α subunit of the IFNα receptor upon IFNα2 binding. One cell line with deletion of the IFNA/B genes showed impaired downmodulation of the IFNα receptor. The data presented here suggest that selection against the IFNα/β system could play a role or accompany the development of the malignant phenotype.
ASJC Scopus subject areas
- Cell Biology