6-mercaptopurine influences TPMT gene transcription in a TPMT gene promoter variable number of tandem repeats-dependent manner.
Pharmacogenomics
; 13(3): 283-95, 2012 Feb.
Article
em En
| MEDLINE
| ID: mdl-22304581
ABSTRACT
AIM:
TPMT activity is characterized by a trimodal distribution, namely low, intermediate and high methylator. TPMT gene promoter contains a variable number of GC-rich tandem repeats (VNTRs), namely A, B and C, ranging from three to nine repeats in length in an A(n)B(m)C architecture. We have previously shown that the VNTR architecture in the TPMT gene promoter affects TPMT gene transcription. MATERIALS, METHODS &RESULTS:
Here we demonstrate, using reporter assays, that 6-mercaptopurine (6-MP) treatment results in a VNTR architecture-dependent decrease of TPMT gene transcription, mediated by the binding of newly recruited protein complexes to the TPMT gene promoter, upon 6-MP treatment. We also show that acute lymphoblastic leukemia patients undergoing 6-MP treatment display a VNTR architecture-dependent response to 6-MP.CONCLUSION:
These data suggest that the TPMT gene promoter VNTR architecture can be potentially used as a pharmacogenomic marker to predict toxicity due to 6-MP treatment in acute lymphoblastic leukemia patients.
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Base de dados:
MEDLINE
Assunto principal:
Transcrição Gênica
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Repetições Minissatélites
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Leucemia-Linfoma Linfoblástico de Células Precursoras
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Mercaptopurina
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Metiltransferases
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article