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 lymphoblastic leukemia (ALL) cell lines to Adriamycin (ADR) was investigated. ADR-sensitive cell lines were found to have wild-type (wt) p53, whereas resistant 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 resistant cells, however, after ADR treatment a 6- to 20-fold dose-dependent increase in wt p53 was observed, whereas mutant p53 increased only twofold. The percentage of apoptotic cells in ADR-sensitive lines with wt p53 ranged from 43 to 93% following ADR treatment, whereas that in resistant lines with 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 mutant p53. These results suggest that p53 gene status and the ability of p53 to induce apoptosis may be determinants of sensitivity to ADR in childhood ALL cells.
Lam
V
V
Department of Pharmacology, University of Toronto, Ontario, Canada.
McPherson
J P
JP
Salmena
L
L
Lees
J
J
Chu
W
W
Sexsmith
E
E
Hedley
D W
DW
Freedman
M H
MH
Reed
J C
JC
Malkin
D
D
Goldenberg
G J
GJ
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004317:Doxorubicin / Q000494:pharmacology* / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D006801:Humans; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004317:Doxorubicin