Mutation of the p53 gene in human acute myelogenous leukemia

Joyce M Slingerland, Mark D. Minden, Samuel Benchimol

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

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 (t1/2). 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 t1/2 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 t1/2 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.

Original languageEnglish
Pages (from-to)1500-1507
Number of pages8
JournalBlood
Volume77
Issue number7
StatePublished - Apr 1 1991
Externally publishedYes

Fingerprint

p53 Genes
Acute Myeloid Leukemia
Genes
Mutation
Codon
Proteins
Valine
Point Mutation
Complementary DNA
Alleles
Cells
Electrophoresis
Aspartic Acid
Methionine
Serine
Cysteine
Half-Life
Disease Progression
Leukemia
Stem Cells

ASJC Scopus subject areas

  • Hematology

Cite this

Slingerland, J. M., Minden, M. D., & Benchimol, S. (1991). Mutation of the p53 gene in human acute myelogenous leukemia. Blood, 77(7), 1500-1507.

Mutation of the p53 gene in human acute myelogenous leukemia. / Slingerland, Joyce M; Minden, Mark D.; Benchimol, Samuel.

In: Blood, Vol. 77, No. 7, 01.04.1991, p. 1500-1507.

Research output: Contribution to journalArticle

Slingerland, JM, Minden, MD & Benchimol, S 1991, 'Mutation of the p53 gene in human acute myelogenous leukemia', Blood, vol. 77, no. 7, pp. 1500-1507.
Slingerland JM, Minden MD, Benchimol S. Mutation of the p53 gene in human acute myelogenous leukemia. Blood. 1991 Apr 1;77(7):1500-1507.
Slingerland, Joyce M ; Minden, Mark D. ; Benchimol, Samuel. / Mutation of the p53 gene in human acute myelogenous leukemia. In: Blood. 1991 ; Vol. 77, No. 7. pp. 1500-1507.
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