Details

Autor(en) / Beteiligte

• Kotur, Nikola
• Stankovic, Biljana
• Kassela, Katerina
• Georgitsi, Marianthi
• Vicha, Anna
• Leontari, Iliana
• Dokmanovic, Lidija
• Janic, Dragana
• Krstovski, Nada
• Klaassen, Kristel
• Radmilovic, Milena
• Stojiljkovic, Maja
• Nikcevic, Gordana
• Simeonidis, Argiris
• Sivolapenko, Gregory
• Pavlovic, Sonja
• Patrinos, George P
• Zukic, Branka

Titel

6-mercaptopurine influences

Ist Teil von

• Pharmacogenomics, 2012-02, Vol.13 (3), p.283-295

Ort / Verlag

Future Medicine Ltd

Erscheinungsjahr

2012

Beschreibungen/Notizen

• TPMT activity is characterized by a trimodal distribution, namely low, intermediate and high methylator. 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 B C architecture. We have previously shown that the VNTR architecture in the gene promoter affects gene transcription. Here we demonstrate, using reporter assays, that 6-mercaptopurine (6-MP) treatment results in a VNTR architecture-dependent decrease of gene transcription, mediated by the binding of newly recruited protein complexes to the 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. These data suggest that the 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. Original submitted 27 July 2011; Revision submitted 24 October 2011