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

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

Author Lopes, L. F. Google Scholar
Piccoli, FDS Google Scholar
Paixao, V. A. Google Scholar
Latorre, MDRDO Google Scholar
Camargo, B. de Google Scholar
Simpson, AJG Google Scholar
Caballero, O. L. Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Ludwig Inst Canc Res
Universidade de São Paulo (USP)
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.
Keywords CYP3A4
V gamma/J beta trans-rearrangements
acute lymphoblastic leukemia
secondary leukemia
genotoxicity
Language English
Date 2004-12-01
Published in Leukemia Research. Oxford: Pergamon-Elsevier B.V., v. 28, n. 12, p. 1281-1286, 2004.
ISSN 0145-2126 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 1281-1286
Origin http://dx.doi.org/10.1016/j.leukres.2004.04.014
Access rights Closed access
Type Article
Web of Science ID WOS:000224780200007
URI http://repositorio.unifesp.br/handle/11600/28039

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