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6-mercaptopurine influences TPMT gene transcription in a TPMT gene promoter variable number of tandem repeats-dependent manner

Kotur, Nikola; Stanković, Biljana; Klaassen, Kristel; Georgitsi, Marianthi; Vicha, Anna; Leontari, Iliana; Dokmanović, Lidija; Janić, Dragana; Krstovski, Nada; Karan-Đurašević, Teodora; Ugrin, Milena; Stojiljković, Maja; Nikčević, Gordana; Simeonidis, Argiris; Sivolapenko, Gregory; Pavlović, Sonja; Partinos, George P.; Zukić, Branka

(Future Medicine Ltd, London, 2012)

TY  - JOUR
AU  - Kotur, Nikola
AU  - Stanković, Biljana
AU  - Klaassen, Kristel
AU  - Georgitsi, Marianthi
AU  - Vicha, Anna
AU  - Leontari, Iliana
AU  - Dokmanović, Lidija
AU  - Janić, Dragana
AU  - Krstovski, Nada
AU  - Karan-Đurašević, Teodora
AU  - Ugrin, Milena
AU  - Stojiljković, Maja
AU  - Nikčević, Gordana
AU  - Simeonidis, Argiris
AU  - Sivolapenko, Gregory
AU  - Pavlović, Sonja
AU  - Partinos, George P.
AU  - Zukić, Branka
PY  - 2012
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/554
AB  - 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.
PB  - Future Medicine Ltd, London
T2  - Pharmacogenomics
T1  - 6-mercaptopurine influences TPMT gene transcription in a TPMT gene promoter variable number of tandem repeats-dependent manner
EP  - 295
IS  - 3
SP  - 283
VL  - 13
DO  - 10.2217/PGS.11.153
ER  - 
@article{
author = "Kotur, Nikola and Stanković, Biljana and Klaassen, Kristel and Georgitsi, Marianthi and Vicha, Anna and Leontari, Iliana and Dokmanović, Lidija and Janić, Dragana and Krstovski, Nada and Karan-Đurašević, Teodora and Ugrin, Milena and Stojiljković, Maja and Nikčević, Gordana and Simeonidis, Argiris and Sivolapenko, Gregory and Pavlović, Sonja and Partinos, George P. and Zukić, Branka",
year = "2012",
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.",
publisher = "Future Medicine Ltd, London",
journal = "Pharmacogenomics",
title = "6-mercaptopurine influences TPMT gene transcription in a TPMT gene promoter variable number of tandem repeats-dependent manner",
pages = "295-283",
number = "3",
volume = "13",
doi = "10.2217/PGS.11.153"
}
Kotur, N., Stanković, B., Klaassen, K., Georgitsi, M., Vicha, A., Leontari, I., Dokmanović, L., Janić, D., Krstovski, N., Karan-Đurašević, T., Ugrin, M., Stojiljković, M., Nikčević, G., Simeonidis, A., Sivolapenko, G., Pavlović, S., Partinos, G. P.,& Zukić, B.. (2012). 6-mercaptopurine influences TPMT gene transcription in a TPMT gene promoter variable number of tandem repeats-dependent manner. in Pharmacogenomics
Future Medicine Ltd, London., 13(3), 283-295.
https://doi.org/10.2217/PGS.11.153
Kotur N, Stanković B, Klaassen K, Georgitsi M, Vicha A, Leontari I, Dokmanović L, Janić D, Krstovski N, Karan-Đurašević T, Ugrin M, Stojiljković M, Nikčević G, Simeonidis A, Sivolapenko G, Pavlović S, Partinos GP, Zukić B. 6-mercaptopurine influences TPMT gene transcription in a TPMT gene promoter variable number of tandem repeats-dependent manner. in Pharmacogenomics. 2012;13(3):283-295.
doi:10.2217/PGS.11.153 .
Kotur, Nikola, Stanković, Biljana, Klaassen, Kristel, Georgitsi, Marianthi, Vicha, Anna, Leontari, Iliana, Dokmanović, Lidija, Janić, Dragana, Krstovski, Nada, Karan-Đurašević, Teodora, Ugrin, Milena, Stojiljković, Maja, Nikčević, Gordana, Simeonidis, Argiris, Sivolapenko, Gregory, Pavlović, Sonja, Partinos, George P., Zukić, Branka, "6-mercaptopurine influences TPMT gene transcription in a TPMT gene promoter variable number of tandem repeats-dependent manner" in Pharmacogenomics, 13, no. 3 (2012):283-295,
https://doi.org/10.2217/PGS.11.153 . .
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