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Bcl-2 Inhibits T-Cell-mediated Cytolysis of a Leukemia Cell Line¹

Oncogene & Tumor Suppressor Gene Program, La Jolla Cancer Research Foundation, La Jolla, California 92037

The bcl-2 gene becomes dysregulated in its expression in a wide variety of human cancers and has been shown to block both spontaneous and drug-induced cell death, thus conferring a selective survival advantage on malignant cells. The biochemical mechanism by which bcl-2 promotes cell survival remains enigmatic but appears to involve a downstream event in an evolutionarily conserved cell death pathway. Here we report that gene transfermediated increases in Bcl-2 protein levels in the human leukemia line Jurkat render these cells more resistant to induction of DNA fragmentation and cytolysis by a cloned T-cell. The killing mechanism used by these particular T-cells was consistent with apoptosis, as opposed to necrosis, in that DNA degradation occurred as a prelysis event. The findings raise the possibility that dysregulation of bcl-2 gene expression could play a role in the avoidance of immune surveillance mechanisms by cancer cells.

¹ This study was supported in part by American Cancer Society Grant IM-708 and NIH Grant CA-54957.

² Present address: Department of Periodontics, School of Dentistry, University of Michigan, Ann Arbor, MI 48109.

³ To whom requests for reprints should be addressed, at Oncogene & Tumor Suppressor Gene Program, La Jolla Cancer Research Foundation, 10901 North Torrey Pines Road, La Jolla, CA 92037.

⁴ Scholar of the Leukemia Society of America.

Received 6/20/94. Accepted 8/ 1/94.

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