Genetic polymorphisms to analyze and predict treatment-related adverse effects in children with acute lymphoblastic leukemia

一些患有急性淋巴母细胞白血病（ALL）或淋巴母细胞淋巴瘤（LBL）的儿童会出现临床重要的治疗相关不良反应。在本研究中，为了确定在维持期影响治疗相关肝毒性风险的新的潜在基因位点，对日本ALL或LBL儿童进行了全基因组基因分型分析。全基因组基因分型共发现28个候选snp。Rho gtpase - activation protein 24 （ARHGAP24）中的rs1966862基因是最显著的候选基因，rs7403531 （RASGRP1）基因型和一些基因也与严重肝毒性显著相关。本研究提示rs1966862 （ARHGAP24）和其他snp可能是ALL或LBL患儿维持期药物性肝毒性的预测因素。

Some children with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL) experience clinically important treatment-related adverse effects. In the present study, to identify novel potential loci influencing the risk of treatment-related hepatotoxicity during the maintenance phase, a genome-wide genotyping analysis was performed in Japanese children with ALL or LBL. Genome-wide genotyping uncovered a total of 28 candidate SNPs. rs1966862, in Rho GTPase-activating protein 24 (ARHGAP24), was the most significant of the candidates, and the genotypes of rs7403531 (RASGRP1) and some genes were also significantly associated with severe hepatotoxicity. This study suggested rs1966862 (ARHGAP24) and the other SNPs to be predictive factors for drug-induced hepatotoxicity during the maintenance phase in pediatric patients with ALL or LBL.