Variants in vincristine pharmacodynamic genes involved in neurotoxicity at induction phase in the therapy of pediatric acute lymphoblastic leukemia.,The Pharmacogenomics Journal

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Variants in vincristine pharmacodynamic genes involved in neurotoxicity at induction phase in the therapy of pediatric acute lymphoblastic leukemia.
The Pharmacogenomics Journal ( IF 2.9 ) Pub Date : 2019-02-06 , DOI: 10.1038/s41397-019-0081-5
Idoia Martin-Guerrero ₁ , Angela Gutierrez-Camino ₁ , Aizpea Echebarria-Barona _{2,

3} , Itziar Astigarraga _{2,

3,

4} , Nagore Garcia de Andoin ₅ , Aurora Navajas _{3,

4} , Africa Garcia-Orad _{1,

3}

Affiliation

Vincristine is an important drug of acute lymphoblastic leukemia (ALL) treatment protocols that can cause neurotoxicity. Patients treated with LAL/SHOP protocols often suffer from vincristine-related neurotoxicity in early phases of treatment. A genetic variant in CEP72, a gene involved in vincristine pharmacodynamics, was recently associated with neurotoxicity after prolonged vincristine treatment. This association was not replicated in our Spanish population during induction phase. To test the possibility that other variants in genes involved in vincristine pharmacodynamics were associated with vincristine neuropathy in early phases of the treatment, we evaluated the correlation with toxicity of 24 polymorphisms in 9 key genes in a large cohort of 152 Spanish children with B-ALL homogeneously treated. Results showed no association between any genetic variant in the TUBB1, TUBB2A, TUBB2B, TUBB3, TUBB4, MAPT, MIR146a, MIR202, and MIR411 genes and vincristine-related neurotoxicity. These results are in line with the hypothesis that there are different mechanisms causing pheripheral neurotoxicity after prolonged and short-term vincristine treatments.

中文翻译：

长春新碱药效学基因变异涉及小儿急性淋巴细胞白血病治疗诱导期的神经毒性。

长春新碱是急性淋巴细胞白血病 (ALL) 治疗方案的重要药物，可引起神经毒性。接受 LAL/SHOP 方案治疗的患者在治疗的早期阶段经常遭受与长春新碱相关的神经毒性。CEP72 中的一个遗传变异是一种参与长春新碱药效学的基因，最近与长期长春新碱治疗后的神经毒性有关。这种关联在我们的西班牙人群中没有在诱导阶段复制。为了测试参与长春新碱药效学的其他基因变异在治疗早期与长春新碱神经病变相关的可能性，我们在一个由 152 名西班牙 B-ALL 儿童组成的大型队列中评估了 9 个关键基因中 24 个多态性与毒性的相关性均匀处理。结果显示，TUBB1、TUBB2A、TUBB2B、TUBB3、TUBB4、MAPT、MIR146a、MIR202 和 MIR411 基因中的任何遗传变异与长春新碱相关的神经毒性之间没有关联。这些结果与长期和短期长春新碱治疗后有不同机制引起外周神经毒性的假设一致。

更新日期：2019-11-18

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