p53 gene status and chemosensitivity of childhood acute lymphoblastic leukemia cells to adriamycin

The role of p53 as a determinant of sensitivity of ten childhood acute lymp hoblastic leukemia (ALL) cell lines to Adriamycin (ADR) was investigated. A DR-sensitive cell lines were found to have wild-type (wt) p53, whereas resi stant cell lines contained point mutations in the gene. The basal level of wt p53 protein in sensitive cells was lower than that of mutant p53 in resi stant cells, however, after ADR treatment a 6- to 20-fold dose-dependent in crease in wt p53 was observed, whereas-mutant p53 increased only twofold. T he percentage of apoptotic cells in ADR-sensitive lines with wt p53 ranged from 43 to 93% following ADR treatment, whereas that in resistant lines wit h mutant p53 was only 8-13%. The ratio of constitutive levels of Bax/Bcl-2 was significantly higher in cells containing wt p53 than in cells with muta nt p53. These results suggest that p53 gene status and the ability of p53 t o induce apoptosis may be determinants of sensitivity to ADR in childhood A LL cells. (C) 1999 Elsevier Science Ltd. All rights reserved.