Induction of 2',5'-oligoadenylate synthetase and blast transformation in primary chronic lymphocytic leukemia cells following exposure to interferon in vitro.

Interferon (IFN) can induce blast transformation and differentiation of malignant cells from patients with chronic lymphocytic leukemia (CLL). In this work the capacity of IFN to induce 2',5'-oligoadenylate synthetase (2',5'-A synthetase) in lymphoid cells from patients with CLL was investigated, and the results were related to the induction of blast transformation. IFN induced enhanced levels of 2',5'-A synthetase in unseparated lymphoid cells from 18 of 24 patients with CLL. In a control group of 11 healthy donors, 2',5'-A synthetase was induced in all cases tested. There was a close correlation between induction of 2',5'-A synthetase and induction of blast transformation by IFN. Thus, transformation occurred in clones expressing enhanced levels of 2',5'-A synthetase, but not in those showing no increase in 2',5'-A synthetase. An enhancement of 2',5'-A synthetase was observed in the IFN-sensitive cells following exposure to concentrations as low as 0.5 IFN units/ml. For induction of blast transformation, 10-1000 times more IFN was required. One h of pretreatment was sufficient for induction of 2',5'-A synthetase, whereas 20 h of pretreatment were required for induction of transformation by IFN. The finding that induction of 2',5'-A synthetase parallels interferon-induced blast transformation indicates that the reason why some CLL clones do not differentiate following exposure to IFN is a resistance of these cells to the action of IFN. The resistance to IFN in some CLL clones may be due to a defect in the 2',5'-A synthetase system of the cells, but it could also be at an early stage of the interaction between IFN and the cell, for instance at the receptor level.