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Induction of 2',5'-Oligoadenylate Synthetase and Blast Transformation in Primary Chronic Lymphocytic Leukemia Cells following Exposure to Interferon in Vitro¹

Radiumhemmet, Karolinska Hospital, 104 01 Stockholm [L. Ö., S. E.], an Department of Clinical Immunology and Division of Clinical Hematology and Oncology, Department of Medicine, Huddinge Hospital and Karolinska Institute, Stockholm [K-H. R.], Sweden

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.

¹ This study was supported by grants from the Swedish Cancer Society and the Cancer Society of Stockholm.

² To whom requests for reprints should be addressed.

Received 5/10/85. Revised 9/ 3/85. Accepted 12/27/85.