Primary leukemia cells resistant to a-interferon in vitro are defective in the activation of the DNA-binding factor interferon-stimulated gene factor 3

Cells from one-third of chronic lymphocytic leukemia (CLL) patients are resistant to a-interferon (a-IFN) as measured by induction of blast transformation. We have previously shown that all CLL clones express a/a-IFN receptors, but that the resistant cells are defective in the induction of the enzyme 2',5'-oligoadenylate synthetase (2',5-A synthetase). Thus, the deficiency in IFN sensitivity is localized somewhere between the interaction of the IFN molecule with its receptor and induction of 2',5'-A synthetase. We have now further characterized the resistance of CLL clones to IFN by investi-gating whether it is associated with a defect in the activation of IFN-stimulated gene factor 3 (ISGF3). which is involved NTERF%RONS (IFNs) are a family of proteins that are produced by eukaryotic cells when challenged by viruses and other agents. Binding of IFNs to specific cell surfac