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Suppression of Acute Lymphoblastic Leukemia by the Human Wild-Type p53 Gene¹

UCSD Cancer Center, Departments of Pathology, Pediatrics, and Biology, University of California, San Diego, La Jolla, California 92093-0063

Independent mutations in both alleles of the p53 tumor suppressor gene are a frequent finding in human T-cell acute lymphoblastic leukemia (T-ALL) cell lines and in the cells of some T-ALL patients in relapse. One major goal of studying the status of p53 (and other tumor suppressor genes) in human cancer is to facilitate the suppression of the tumorigenic phenotype through the restoration of the expression of the wild-type allele. While the efficient insertion of a suppressor into all cells of solid/metastatic human tumors may at present be impossible, insertion into leukemia cells may be feasible due to the accessibility of the leukemia cells in the body. To examine the feasibility of suppressing the tumorigenicity of human T-leukemia cells, the human T-ALL cell line Be-13, which lacks endogenous p53 protein, was infected with a recombinant retrovirus encoding the wild-type allele of human p53 (hwtp53). Expression of p53 reduced the growth rate of infected Be-13 cells in vitro, suppressed colony formation in methylcellulose cultures, and abrogated their tumorigenic phenotype in nude mice in vivo. These results suggest that suppression of the leukemic phenotype of relapse T-ALL-derived Be-13 cells is feasible. Acute leukemia cell suppression via high-efficiency infection with retroviruses encoding wtp53 may be feasible and beneficial in T-ALL cases as part of a bone marrow transplantation regimen in an effort to reduce the frequency of posttransplantation relapse.

¹ This work was supported by Grant 465A awarded by the American Cancer Society and by grants from the NIH.

² The first two authors of this paper have had similar input into its content, and should be regarded as equal, first authors.

³ To whom requests for reprints should be addressed, at Department of Biology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0063.

Received 9/18/91. Accepted 11/ 8/91.