在儿童急性淋巴细胞白血病患者的维持治疗期间，TPMT基因表达以TPMT基因启动子串联重复序列可变数目依赖的方式增加。
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.
作者信息
Kotur Nikola, Dokmanovic Lidija, Janic Dragana, Stankovic Biljana, Krstovski Nada, Tosic Natasa, Katsila Theodora, Patrinos George P, Zukic Branka, Pavlovic Sonja
机构信息
Laboratory for Molecular Biomedicine, Institute of Molecular Genetics & Genetic Engineering, University of Belgrade, Serbia.
University Children's Hospital, School of Medicine, University of Belgrade, Serbia.
出版信息
Pharmacogenomics. 2015;16(15):1701-12. doi: 10.2217/pgs.15.109. Epub 2015 Sep 28.
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.
目的
6-巯基嘌呤以依赖于硫嘌呤甲基转移酶（TPMT）启动子可变串联重复序列（VNTR）的方式影响体外TPMT基因表达。我们研究了6-巯基嘌呤和甲氨蝶呤给药后儿童急性淋巴细胞白血病（ALL）患者的TPMT表达以及VNTR结构的药物基因组学潜力。
材料与方法
在诊断时（n = 57）和维持治疗期间（n = 27）测定儿童ALL患者的TPMT基因表达。
结果
维持治疗期间TPMT基因表达增加了三倍，受VNTR区域结构的调节。
结论
在儿童ALL患者维持治疗开始时就需要考虑TPMT启动子基因变异。在引入硫嘌呤治疗时，TPMT启动子VNTR区域可作为药物基因组学生物标志物。
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