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首页> 外文期刊>Pharmacogenomics and Personalized Medicine >Thiopurine S-methyltransferase polymorphisms in acute lymphoblastic leukemia, inflammatory bowel disease and autoimmune disorders: influence on treatment response
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Thiopurine S-methyltransferase polymorphisms in acute lymphoblastic leukemia, inflammatory bowel disease and autoimmune disorders: influence on treatment response

机译：硫代嘌呤S-甲基转移酶基因多态性在急性淋巴细胞白血病，炎性肠病和自身免疫性疾病中：对治疗反应的影响

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The thiopurine S-methyltransferase ( TPMT ) gene encodes for the TPMT enzyme that plays a crucial role in the metabolism of thiopurine drugs. Genetic polymorphisms in this gene can affect the activity of the TPMT enzyme and have been correlated with variability in response to treatment with thiopurines. Advances in the pharmacogenetics of TPMT allowed the development of dosing recommendations and treatment strategies to optimize and individualize prescribing thiopurine in an attempt to enhance treatment efficacy while minimizing toxicity. The influence of genetic polymorphisms in the TPMT gene on clinical outcome has been well-documented and replicated in many studies. In this review, we provide an overview of the evolution, results, conclusions and recommendations of selected studies that investigated the influence of TPMT pharmacogenetics on thiopurine treatment in acute lymphoblastic leukemia, inflammatory bowel disease and autoimmune disorders. We focus mainly on prospective studies that explored the impact of individualized TPMT-based dosing of thiopurines on clinical response. Together, these studies demonstrate the importance of preemptive TPMT genetic screening and subsequent dose adjustment in mitigating the toxicity associated with thiopurine treatment while maintaining treatment efficacy and favorable long-term outcomes. In addition, we briefly address the cost-effectiveness of this pharmacogenetics approach and its impact on clinical practice as well as the importance of recent breakthrough advances in sequencing and genotyping techniques in refining the TPMT genetic screening process.
机译：硫嘌呤S-甲基转移酶（TPMT）基因编码在硫嘌呤药物代谢中起关键作用的TPMT酶。该基因的遗传多态性可影响TPMT酶的活性，并已与硫嘌呤治疗反应的变异性相关。 TPMT药理遗传学的进展允许制定剂量建议和治疗策略，以优化和个性化处方硫代嘌呤，以期在最大程度降低毒性的同时提高治疗效果。 TPMT基因中遗传多态性对临床结局的影响已得到充分证明，并在许多研究中得到了重复。在这篇综述中，我们概述了一些研究的进展，结果，结论和建议，这些研究调查了TPMT药物遗传学对硫代嘌呤治疗急性淋巴细胞白血病，炎性肠病和自身免疫性疾病的影响。我们主要侧重于前瞻性研究，这些研究探讨了基于TPMT的个体化硫嘌呤给药对临床反应的影响。总之，这些研究表明，先进行TPMT基因筛查和随后的剂量调整在减轻与硫嘌呤治疗有关的毒性的同时保持治疗效力和良好的长期结果的重要性。此外，我们简要介绍了这种药物遗传学方法的成本效益及其对临床实践的影响，以及测序和基因分型技术的最新突破性进展对完善TPMT基因筛选过程的重要性。

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