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

Autor 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
Instituição Universidade Federal de São Paulo (UNIFESP)
Ludwig Inst Canc Res
Universidade de São Paulo (USP)
Resumo 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.
Palavra-chave CYP3A4
V gamma/J beta trans-rearrangements
acute lymphoblastic leukemia
secondary leukemia
genotoxicity
Idioma Inglês
Data de publicação 2004-12-01
Publicado em Leukemia Research. Oxford: Pergamon-Elsevier B.V., v. 28, n. 12, p. 1281-1286, 2004.
ISSN 0145-2126 (Sherpa/Romeo, fator de impacto)
Publicador Elsevier B.V.
Extensão 1281-1286
Fonte http://dx.doi.org/10.1016/j.leukres.2004.04.014
Direito de acesso Acesso restrito
Tipo Artigo
Web of Science WOS:000224780200007
Endereço permanente http://repositorio.unifesp.br/handle/11600/28039

Exibir registro completo




Arquivo

Arquivo Tamanho Formato Visualização

Não existem arquivos associados a este item.

Este item está nas seguintes coleções

Buscar


Navegar

Minha conta