WILD-TYPE P53 INDUCES APOPTOSIS OF MYELOID LEUKEMIC-CELLS THAT IS INHIBITED BY INTERLEUKIN-6

WILD-TYPE p53 protein has many properties consistent with its being the product of a tumour suppressor gene 1-3. Although the normal roles of tumour suppressor genes are still largely unknown, it seems that they could be involved in promoting cell differentiation 4-6 as well as in mediating growth arrest by growth-inhibitory cytokines 7-9. Hence, the abrogation of wild-type p53 expression, which is a common feature of many tumours, could eliminate these activities. We have now tested this notion by restoring the expression of p53 in a murine myeloid leukaemic cell line that normally lacks p53. The use of a temperature-sensitive p53 mutant 10 allowed us to analyse cells in which the introduced p53 had either wild-type or mutant properties. Although there seemed to be no effect on differentiation, the introduction of wild-type p53 resulted in rapid loss of cell viability in a way characteristic of apoptosis (programmed cell death). The effect of wild-type p53 was counteracted by interleukin-6. Thus products of tumour suppressor genes could be involved in restricting precursor cell populations by mediating apoptosis.