Ohio State University, Columbus, Ohio, USA.
Indiana University School of Medicine, Indianapolis, Indiana, USA.
Clin Pharmacol Ther. 2019 Jun;105(6):1421-1428. doi: 10.1002/cpt.1324. Epub 2019 Jan 21.
Vincristine is one of the core chemotherapy agents used in the treatment of pediatric acute lymphoblastic leukemia (ALL). However, one of the major toxicities resulting from vincristine exposure is vincristine-induced peripheral neuropathy (VIPN). When VIPN results in significant morbidity, the vincristine dose may need to be reduced, thus potentially decreasing the effectiveness of treatment. To date, there are no robust biomarkers used clinically to determine which patients will be at risk for worse neuropathy. The current study included genomewide association study (GWAS) in two independent cohorts: Pediatric Oncology Group (POG) ALL trials and a multicenter study based at Indiana University in children with ALL. A meta-analysis of the cohorts identified two single-nucleotide polymorphisms (SNPs), rs1045644 and rs7963521, as being significantly (P value threshold 0.05/4749 = 1.05E-05) associated with neuropathy. Subsequently these SNPs may be effective biomarkers of VIPN in children with ALL.
长春新碱是治疗小儿急性淋巴细胞白血病（ALL）的核心化疗药物之一。然而，长春新碱暴露引起的主要毒性之一是长春新碱诱导的周围神经病变（VIPN）。当 VIPN 导致显著的发病率时，可能需要降低长春新碱剂量，从而降低治疗的有效性。迄今为止，临床上尚无用于确定哪些患者存在更严重神经病变风险的强大生物标志物。本研究包括两个独立队列的全基因组关联研究（GWAS）：儿科肿瘤学组（POG）ALL 试验和印第安纳大学的多中心 ALL 儿童研究。对这些队列的荟萃分析确定了两个单核苷酸多态性（SNP），rs1045644 和 rs7963521，与神经病变显著相关（P 值阈值 0.05/4749=1.05E-05）。随后，这些 SNP 可能是 ALL 儿童 VIPN 的有效生物标志物。
