Alpha-interferon receptors in malignant B-cells from patients with chronic lymphocytic leukemia: relation to induction of 2'-5'-oligoadenylate synthetase and blast transformation.

alpha-Interferon (IFN-alpha) induces blast transformation of malignant B-cells from approximately 65% of chronic lymphocytic leukemia patients. We have shown previously that induction of blast transformation correlates with induction of 2'-5'-oligoadenylate synthetase. In this paper we address the question of whether low responsiveness to IFN-alpha is associated with a reduced expression of the IFN receptor. IFN-alpha receptor expression was studied by the binding of radioiodinated IFN-alpha to peripheral blood malignant B-cells from 20 chronic lymphocytic leukemia patients and to blood cells from 5 healthy donors. Chronic lymphocytic leukemia cells from all 20 patients displayed high affinity IFN-alpha receptors [mean Kd, 62 +/- 9 (SE) pM] ranging between 110 and 850 binding sites/cell [mean, 416 +/- 51]. Nonmalignant mononuclear blood cells showed similar binding data (411 +/- 105 binding sites/cell; Kd 66 +/- 20 pM). Receptor expression did not correlate with the degree of blast transformation or with induction of 2'-5'-oligoadenylate synthetase. We conclude that the deficiency of IFN sensitivity is localized somewhere between signal transduction from the receptor and induction of 2'-5'-oligoadenylate synthetase.