WT-P53 ACTION IN HUMAN LEUKEMIA-CELL LINES CORRESPONDING TO DIFFERENTSTAGES OF DIFFERENTIATION

Recent studies support the potential application of the wt-p53 gene in cancer therapy. Expression of exogenous wt-p53 suppresses a variety o f leukaemia phenotypes by acting on cell survival, proliferation and/o r differentiation. As for tumour gene therapy, the final fate of the n eoplastic cells is one of the most relevant points. We examined the ef fects of exogenous wt-p53 gene expression in several leukaemia cell li nes to identify p53-responsive leukaemia. The temperature-sensitive p5 3(Val135) mutant or the human wt-p53 cDNA was transduced in leukaemia cell lines representative of different acute leukaemia FAB subtypes, i ncluding M1 (KG1), M2 (HL-60), M3 (NB4), M5 (U937) and M6 (HEL 92.1.7) , as well as blast crisis of chronic myelogenous leukaemia (BC-CML: K5 62, BV173) showing diverse differentiation features. By morphological, molecular and biochemical analyses, we have shown that exogenous wt-p 53 gene expression induces apoptosis only in cells corresponding to M1 , M2 and M3 of the FAB classification and in BC-CML showing morphologi cal and cytochemical features of undifferentiated blast cells. In cont rast. it promotes differentiation in the others. Interestingly, cell r esponsiveness was independent of the vector used and the status of the endogenous p53 gene.