Hemizygous expression of the wild-type p53 allele may confer a selective growth advantage before complete inactivation of the p53 gene in the progression of chronic myelogenous leukaemia.
We analysed the expression of the p53 gene in various clinical phases of chronic myelogenous leukaemia (CML) by quantitative reverse transcriptase (RT) polymerase chain reaction (PCR). Hemizygous expression of the wild-type p53 allele was observed in two samples showing the loss of one p53 allele, and affected p53 expression was associated with p53 allelic loss rather than the clinical phase of CML. In four patients with CML showing p53 inactivation, we performed a detailed sequential analysis of p53 allelic loss, p53 mutation and expression from the onset of the disease to the patients' death. Consequently, we demonstrated that the loss of a wild-type p53 allele preceded mutation of the remaining allele, and that cells hemizygous for the wild-type p53 allele dominated those with both wild-type alleles, then were replaced by cells with complete p53 inactivation. These observations indicate that not only complete p53 inactivation but also hemizygous expression of the wild-type p53 allele may confer a selective growth advantage, and that the former is implicated in a more malignant phase than the latter. Alternatively, the inactivation of another undefined anti-oncogene on chromosome 17p may allow selective growth before the p53 mutation occurs.
Nakai
H
H
Third Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan.
Misawa
S
S
Horiike
S
S
Maekawa
T
T
Kashima
K
K
Ishizaki
K
K
D000483:Alleles; D001483:Base Sequence; D002869:Chromosome Aberrations; D002886:Chromosomes, Human, Pair 17; D018450:Disease Progression; D005500:Follow-Up Studies; D015973:Gene Expression Regulation, Leukemic; D016158:Genes, p53; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000473:pathology; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger