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Title: Association of CYP3A4 genotype with detection of V gamma/J beta trans-rearrangements in the peripheral blood leukocytes of pediatric cancer patients undergoing chemotherapy for ALL
Authors: Lopes, L. F.
Piccoli, FDS
Paixao, V. A.
Latorre, MDRDO
Camargo, B. de
Simpson, AJG
Caballero, O. L.
Universidade Federal de São Paulo (UNIFESP)
Ludwig Inst Canc Res
Universidade de São Paulo (USP)
Keywords: CYP3A4
V gamma/J beta trans-rearrangements
acute lymphoblastic leukemia
secondary leukemia
Issue Date: 1-Dec-2004
Publisher: Elsevier B.V.
Citation: Leukemia Research. Oxford: Pergamon-Elsevier B.V., v. 28, n. 12, p. 1281-1286, 2004.
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 Vgamma/Jbeta 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. (C) 2004 Elsevier B.V. All rights reserved.
ISSN: 0145-2126
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