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Correlation between interferon (IFN) alpha resistance and deletion of the
IFN alpha/beta genes in acute leukemia cell lines suggests selection
against the IFN system
OR Colamonici, P Domanski, LC Platanias and MO Diaz
Section of Hematology/Oncology, University of Chicago, IL 60637-1470.
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 IFN alpha/beta 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 IFN alpha/beta and,
thus, lesions at the receptor or signal transduction level should also be
present to render cells resistant to exogenous IFN alpha/beta. To test if
selection against the IFN system was operating in acute leukemias, the
sensitivity to the antiproliferative effect of IFN alpha 2 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 IFN alpha 2,
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 IFN alpha 2.
No significant alteration in the expression or structure of the IFN alpha
receptor was observed. We also studied the downmodulation of the alpha
subunit of the IFN alpha receptor upon IFN alpha 2 binding. One cell line
with deletion of the IFNA/B genes showed impaired downmodulation of the IFN
alpha receptor. The data presented here suggest that selection against the
IFN alpha/beta system could play a role or accompany the development of the
malignant phenotype.
Volume 80,
Issue 3,
pp. 744-749,
08/01/1992
Copyright © 1992 by The American Society of Hematology
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