Induction of 2',5'-oligoadenylate synthetase and blast transformation in primary chronic lymphocytic leukemia cells following exposure to interferon in vitro
Ostlund, L.; Einhorn, S.; Robèrt, K.H.
Cancer Research 46(4 Part 2): 2160-2163
1986
ISSN/ISBN: 0008-5472 PMID: 2418964 Document Number: 283273
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.