Association of CYP3A4 genotype with detection of Vγ/Jβ trans-rearrangements in the peripheral blood leukocytes of pediatric cancer patients undergoing chemotherapy for ALL

Luiz Fernando Lopes, Fábio De Simone Piccoli, Valéria A. Paixão, Maria Do Rosário D.O. Latorre, Beatriz De Camargo, Andrew J.G. Simpson, Otávia L. Caballero

    Research output: Contribution to journalArticle

    14 Scopus citations

    Abstract

    Cancer patients receiving chemotherapy are exposed to high doses of cytotoxic and genotoxic drugs which, in some cases, can lead to treatment related leukemia. Since this only occurs in a minority of patients, however, it is possible some individuals are predisposed due to genetic polymorphisms in genes for enzymes that mediate drug metabolism. To address this possibility we measured the genotoxicity of chemotherapeutic agents in patients receiving treatment for ALL by the frequency of the Vγ/Jβ trans-rearrangement in their peripheral blood leukocytes and compared this with CYP3A4 genotype. CYP3A4 is the most abundant of the cytochrome P450 (CYP) enzyme in the liver and intestine which contains a common -392A>G substitution in the promoter region (CYP3A4*1B allele). We found a significant increase in the frequency of rearrangements during chemotherapy only in patients homozygous for the wild type CYP3A4*1A allele. This provides a direct link between CYP3A4 genotype and susceptibility to drug genotoxicity thus strengthening the possibility that predisposition to treatment related leukemia may be measurable by simple genetic testing.

    Original languageEnglish (US)
    Pages (from-to)1281-1286
    Number of pages6
    JournalLeukemia Research
    Volume28
    Issue number12
    DOIs
    StatePublished - Dec 1 2004

    Keywords

    • Acute lymphoblastic leukemia
    • CYP3A4
    • Genotoxicity
    • Secondary leukemia
    • Vγ/Jβ Trans-rearrangements

    ASJC Scopus subject areas

    • Hematology
    • Oncology
    • Cancer Research

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  • Cite this

    Lopes, L. F., Piccoli, F. D. S., Paixão, V. A., Latorre, M. D. R. D. O., Camargo, B. D., Simpson, A. J. G., & Caballero, O. L. (2004). Association of CYP3A4 genotype with detection of Vγ/Jβ trans-rearrangements in the peripheral blood leukocytes of pediatric cancer patients undergoing chemotherapy for ALL. Leukemia Research, 28(12), 1281-1286. https://doi.org/10.1016/j.leukres.2004.04.014