The p53 gene in pediatric therapy-related leukemia and myelodysplasia

Carolyn A. Felix, Matthew R. Hosler, Deborah Provisor, Kevin Salhany, Elizabeth A. Sexsmith, Diana J. Slater, Nai Kong V Cheung, Naomi J. Winick, Eric A. Strauss, Ruth Heyn, Beverly J. Lange, David Malkin

Research output: Contribution to journalArticle

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Abstract

We investigated the frequency of p53 mutations in 19 pediatric cases of therapy-related leukemia or myelodysplastic syndrome. Eleven children presented with acute myeloid leukemia, one with mixed-lineage leukemia, two with acute lymphoblastic leukemia, and five with myelodysplasia at times ranging from 11 months to 9 years after a primary cancer diagnosis. The primary cancers, which included 11 solid tumors and eight leukemias, were treated with various combinations of DNA topoisomerase II inhibitors, alkylating agents, or irradiation. Leukemic or myelodysplastic marrows were screened for possible mutations by single-strand conformation polymorphism (SSCP) analysis of p53 exons 4 to 8. The only observed mutation was an inherited 2-basepair deletion at codon 209 in exon 6 that would shift the open reading frame, create a premature termination codon, and foreshorten the resultant protein. Prior therapy in this patient included DNA topoisomerase II inhibitors, alkylating agents, and irradiation. The secondary leukemia presented as myelodysplasia with monosomies of chromosomes 5 and 7 and abnormalities of chromosome 17. Although the primary cancer was an embryonal rhabdomyosarcoma and there was a family history of cancer, the case did not fulfill the clinical criteria for Li-Fraumeni syndrome. This study suggests that germline p53 mutations may predispose some children to therapy-related leukemia and myelodysplasia, but that p53 mutations otherwise are infrequent in this setting.

Original languageEnglish (US)
Pages (from-to)4376-4381
Number of pages6
JournalBlood
Volume87
Issue number10
StatePublished - May 15 1996

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Topoisomerase II Inhibitors
Pediatrics
Alkylating Agents
p53 Genes
Chromosomes
Exons
Leukemia
Genes
Irradiation
Polymorphism
Conformations
Tumors
Neoplasms
Mutation
Li-Fraumeni Syndrome
Embryonal Rhabdomyosarcoma
Therapeutics
Chromosomes, Human, Pair 5
Chromosomes, Human, Pair 17
Germ-Line Mutation

ASJC Scopus subject areas

  • Hematology

Cite this

Felix, C. A., Hosler, M. R., Provisor, D., Salhany, K., Sexsmith, E. A., Slater, D. J., ... Malkin, D. (1996). The p53 gene in pediatric therapy-related leukemia and myelodysplasia. Blood, 87(10), 4376-4381.

The p53 gene in pediatric therapy-related leukemia and myelodysplasia. / Felix, Carolyn A.; Hosler, Matthew R.; Provisor, Deborah; Salhany, Kevin; Sexsmith, Elizabeth A.; Slater, Diana J.; Cheung, Nai Kong V; Winick, Naomi J.; Strauss, Eric A.; Heyn, Ruth; Lange, Beverly J.; Malkin, David.

In: Blood, Vol. 87, No. 10, 15.05.1996, p. 4376-4381.

Research output: Contribution to journalArticle

Felix, CA, Hosler, MR, Provisor, D, Salhany, K, Sexsmith, EA, Slater, DJ, Cheung, NKV, Winick, NJ, Strauss, EA, Heyn, R, Lange, BJ & Malkin, D 1996, 'The p53 gene in pediatric therapy-related leukemia and myelodysplasia', Blood, vol. 87, no. 10, pp. 4376-4381.
Felix CA, Hosler MR, Provisor D, Salhany K, Sexsmith EA, Slater DJ et al. The p53 gene in pediatric therapy-related leukemia and myelodysplasia. Blood. 1996 May 15;87(10):4376-4381.
Felix, Carolyn A. ; Hosler, Matthew R. ; Provisor, Deborah ; Salhany, Kevin ; Sexsmith, Elizabeth A. ; Slater, Diana J. ; Cheung, Nai Kong V ; Winick, Naomi J. ; Strauss, Eric A. ; Heyn, Ruth ; Lange, Beverly J. ; Malkin, David. / The p53 gene in pediatric therapy-related leukemia and myelodysplasia. In: Blood. 1996 ; Vol. 87, No. 10. pp. 4376-4381.
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