Action of interferon-alpha on hairy cell leukemia: Expression of specific receptors and (2′–5′)oligo (a) synthetase in tumor cells from sensitive and resistant patients

IFN- α induces tumor regression with a high percentage of complete remissions in hairy cell leukemia. We have recently reported that hairy cells express specific IFN- α receptors which are down-regulated upon therapy. We show here that the activity of 2–5 A synthetase, an IFN-induced enzyme, is 2 to 7-fold stimulated in hairy cells from responsive patients within 12–24 h after the first IFN dose. This in-vivo enzyme induction paralleled the kinetics of receptor down-regulation. In one patient who was unresponsive to IFN- α treatment neither expression of IFN- α receptor nor change in 2–5 A synthetase could be detected, whereas in a second unresponsive patient, both receptors and 2–5 A synthetase were expressed and modulated as in sensitive patients. In-vitro treatment of hairy cells with recombinant interferons showed that IFN- β1 was able to induce this enzyme to the same extent than IFN- α2, whereas IFN- γ was inactive despite the presence of specific IFN- γ receptors. Our results indicate that IFN- α can exert its therapeutic effects by acting directly on the hairy cells through interaction with surface membrane receptors. Induction of 2–5 A synthetase can be one of the steps involved in this action. However, both mechanisms, as well as receptor down-regulation are not sufficient to explain the responsiveness of hairy cell leukemia to IFN- α.