Role of the p53 tumor suppressor gene in the pathogenesis and in the suppression of acute lymphoblastic T-cell leukemia.
The tumor suppressor gene p53 has been shown to be mutated in 50% of acute lymphoblastic T-cell-leukemia (T-ALL) cell lines, all of which were established from T-ALL cases in relapse. In these lines both alleles of the p53 gene were independently affected by point mutation. In contrast, in human solid tumors possessing a mutated p53 allele, the second wild-type p53 suppressor allele is often lost by deletion rather than altered by mutation. This suggests that in T-ALL cell lines, the product encoded by the second mutated allele provides the cells with an additional oncogenic stimulus, beyond the loss of suppressive activity. While different p53 mutations have been shown to possess differential oncogenic potential in the p53 plus ras cotransformation assay, in T-ALL cells different mutations may in addition possess distinct functions, further contributing to the tumorigenic phenotype.
Yeargin
J
J
Dept. Biology/Cancer Center, UCSD, La Jolla 92093-0063.
Cheng
J
J
Haas
M
M
D000818:Animals; D002872:Chromosome Deletion; D003062:Codon / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics*; D015316:Genetic Therapy; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D012878:Skin Neoplasms / Q000235:genetics; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D003062:Codon; D016159:Tumor Suppressor Protein p53