Azimi F, Jafariyan M, Khatami S, Mortazavi Y, Azad M
M.S.c student of medical genetics, Zanjan University of Medical Science, Zanjan,Iran.
PhD student of molecular medicine, Zanjan University of Medical Science, Zanjan,Iran.
Iran J Ped Hematol Oncol. 2014;4(1):32-8. Epub 2014 Apr 20.
For the past half century, thiopurines have earned themselves a reputation as effective anti-cancer and immunosuppressive drugs. Thiopurine S-methyltransferase (TPMT) is involved in the metabolism of all thiopurines and is one of the main enzymes that inactivates mercaptopurine. 6-MP is now used as a combination therapies for maintenance therapy of children with acute lymphocytic leukemia (ALL). In all patients receiving mercaptopurine, there is a risk of bone marrow suppression. TPMT activity is inherited as a monogenic, co-dominant trait. More than 25 variants are known. Genetic testing is available for several TPMT variant alleles. Most commonly TPMT*2, *3A, and *3C are tested for, which account for >90% of inactivating alleles. Differences in DNA that alter the expression or function of proteins that are targeted by drugs can contribute significantly to variation in the responses of individuals.Genotyping may become part of routine investigations to help clinicians tailor drug treatment effectively. This success is mainly due to the development of combination therapies and stratification of patients according to risk of treatment failure and relapse, rather than the discovery of new drugs. The aim of this study was to investigate the effect of genotype or methyltransferase enzyme activity before starting therapy in children with ALL. This can prevent the side effect of thiopurine drugs. In fact, the common polymorphism of this enzyme in population could be a prognostic factor in relation to drug use and treatment of patients with ALL.
在过去的半个世纪里，硫嘌呤类药物已成为有效的抗癌和免疫抑制药物。硫嘌呤S-甲基转移酶（TPMT）参与所有硫嘌呤类药物的代谢，是使巯嘌呤失活的主要酶之一。6-巯基嘌呤（6-MP）现用于儿童急性淋巴细胞白血病（ALL）维持治疗的联合疗法中。在所有接受巯嘌呤治疗的患者中，都存在骨髓抑制的风险。TPMT活性作为一种单基因共显性性状遗传。已知有超过25种变体。针对几种TPMT变体等位基因的基因检测是可行的。最常检测的是TPMT*2、3A和3C，它们占失活等位基因的90%以上。DNA的差异会改变药物靶向的蛋白质的表达或功能，这可能显著导致个体反应的差异。基因分型可能会成为常规检查的一部分，以帮助临床医生有效地调整药物治疗方案。这一成功主要归功于联合疗法的发展以及根据治疗失败和复发风险对患者进行分层，而非新药的发现。本研究的目的是调查在ALL儿童开始治疗前基因型或甲基转移酶活性的影响。这可以预防硫嘌呤类药物的副作用。事实上，该酶在人群中的常见多态性可能是ALL患者药物使用和治疗的一个预后因素。
