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Mutation of the p53 gene in human acute myelogenous leukemia
JM Slingerland, MD Minden and S Benchimol
Ontario Cancer Institute, Toronto, Canada.
Heterogeneity of p53 protein expression is seen in blast cells of patients
with acute myelogenous leukemia (AML). p53 protein is detected in the
blasts of certain AML patients but not in others. We have identified p53
protein variants with abnormal mobility on gel electrophoresis and/or
prolonged half-life (t 1/2). We have sequenced the p53 coding sequence from
primary blast cells of five AML patients and from the AML cell line
(OCIM2). In OCIM2, a point mutation in codon 274 was identified that
changes a valine residue to aspartic acid. A wild type p53 allele was not
detected in these cells. Two point mutations (codon 135, cysteine to
serine; codon 246, methionine to valine) were identified in cDNA from
blasts of one AML patient. Both mutations were present in blast colonies
grown from single blast progenitor cells, indicating that individual
leukemia cells had sustained mutation of both p53 alleles. The cDNAs
sequenced from blast samples of four other patients, including one with
prolonged p53 protein t 1/2 and one with no detectable p53 protein, were
fully wild type. Thus, the heterogeneity of p53 expression cannot be
explained in all cases by genetic change in the p53 coding sequence. The
prolonged t 1/2 of p53 protein seen in some AML blasts may therefore
reflect changes not inherent to p53. A model is proposed in which
mutational inactivation of p53, although not required for the evolution of
neoplasia, would confer a selective advantage, favoring clonal outgrowth
during disease progression.
Volume 77,
Issue 7,
pp. 1500-1507,
04/01/1991
Copyright © 1991 by The American Society of Hematology
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