TPMT gene expression is increased during maintenance therapy in childhood acute lymphoblastic leukemia patients in a TPMT gene promoter variable number of tandem repeat-dependent manner. (October 2015)

• Record Type: Journal Article
• Authors: Kotur, Nikola; Dokmanovic, Lidija; Janic, Dragana; Stankovic, Biljana; Krstovski, Nada; Tosic, Natasa; Katsila, Theodora; Patrinos, George P; Zukic, Branka; Pavlovic, Sonja
• Is Part Of: Pharmacogenomics. Volume 16:Number 15(2015)
• Page Start: 1701
• Page End: 1712
• Publication Date: 2015-10
• Subjects: 6-mercaptopurine -- childhood acute lymphoblastic leukemia -- maintenance therapy -- pharmacogenomics -- TPMT expression -- TPMT genetic variations -- variable number of tandem repeats -- VNTR; Pharmacogenomics -- Periodicals; 615.1
• DOI: 10.2217/pgs.15.109
• Languages: English
• ISSNs: 1462-2416

Abstract

Aims: 6-mercaptopurine influences in vitro TPMT gene expression in a TPMT promoter variable number of tandem repeats (VNTR)-dependent manner. We studied TPMT expression following 6-mercaptopurine and methotrexate administration in childhood acute lymphoblastic leukemia (ALL) patients and the pharmacogenomic potential of the VNTR architecture.Materials & methods: TPMT gene expression was determined in childhood ALL patients at diagnosis (n = 57) and during the maintenance therapy (n = 27).Results: A threefold increase of TPMT gene expression was obtained during maintenance therapy, modulated by the architecture of the VNTR region.Conclusion: The TPMT promoter genetic variants need to be considered at the very beginning of the maintenance therapy for childhood ALL patients. The TPMT promoter VNTR region may serve as a pharmacogenomic biomarker when introducing thiopurine therapy.