Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Medicine and Nursery, University of the Basque Country (UPV/EHU), Leioa, Spain.
Unit of Pediatric Hematology/Oncology, University Hospital Cruces, Bilbao, Spain.
Pharmacogenomics J. 2019 Dec;19(6):564-569. doi: 10.1038/s41397-019-0081-5. Epub 2019 Feb 6.
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.
长春新碱是急性淋巴细胞白血病（ALL）治疗方案中的重要药物，可引起神经毒性。接受 LAL/SHOP 方案治疗的患者在治疗早期常出现长春新碱相关的神经毒性。最近，长春新碱药效动力学相关基因 CEP72 的一个遗传变异与长期长春新碱治疗后的神经毒性相关。在我们的西班牙人群中，该关联在诱导期并未得到复制。为了验证参与长春新碱药效动力学的其他基因中的变异是否与治疗早期的长春新碱神经病变相关，我们在一个大型的 152 例 B-ALL 西班牙儿童队列中评估了 9 个关键基因中的 24 个多态性与毒性的相关性，这些儿童均接受了同质的治疗。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均无关联。这些结果与以下假设一致，即长期和短期长春新碱治疗后引起周围神经毒性的机制不同。
