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.
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.
Entities:
Keywords:
6-mercaptopurine; TPMT expression; TPMT genetic variations; VNTR; childhood acute lymphoblastic leukemia; maintenance therapy; pharmacogenomics; variable number of tandem repeats