Junghanns Anne-Sophie, Wittig Susan, Woehlecke Caroline, Lehmann Thomas, Arndt Clemens, Gruhn Bernd
Department of Pediatrics, Jena University Hospital, Jena, Germany.
Institute of Medical Statistics, Computer Sciences and Documentation, Jena University Hospital, Jena, Germany.
J Cancer Res Clin Oncol. 2015 Dec;141(12):2221-8. doi: 10.1007/s00432-015-2018-y. Epub 2015 Jul 30.
Wilms tumor gene single nucleotide polymorphism (WT1 SNP) rs16754 has been described as a favorable risk marker in patients with acute myeloid leukemia. Subsequent studies revealed inconsistent results in both adult and pediatric patients. We analyzed its impact on clinical outcome in children with acute lymphoblastic leukemia (ALL) for the first time.
WT1 SNP rs16754 of 158 children with ALL treated according to ALL Berlin-Frankfurt-Münster treatment trials from 1990 to 2009 and 43 hematopoietic stem cell donors was analyzed by allelic discrimination. WT1 SNP status was correlated with disease characteristics and clinical outcome comparing SNP (WT1(GG/AG)) and wildtype (WT1(AA)).
At least one minor allele was found in 23.4 % of patients and 34.9 % of donors (P = 0.07). Distribution of patient and disease characteristics was similar between WT1(GG/AG) and WT1(AA). In multivariate analyses, WT1 SNP was an independent good prognostic marker for cumulative incidence of relapse (CIR WT1(AA) vs. WT1(GG/AG) HR = 3.384, P = 0.021) and event-free survival (EFS; event risk WT1(AA) vs. WT1(GG/AG) HR = 2.503, P = 0.036). Univariate subanalyses of patients who underwent an allogeneic hematopoietic stem cell transplantation revealed more significant differences in CIR (P = 0.017), EFS (P = 0.012), and overall survival (OS; P = 0.017). Donor's WT1 SNP status did not affect outcome. We found no correlation between WT1 SNP and WT1 expression level at diagnosis (P = 0.634).
WT1 SNP rs16754 predicts improved CIR and EFS. Outcome differences were more prominent in transplanted children. Our findings identify WT1 SNP rs16754 as a favorable risk marker in pediatric ALL which is independent from known risk factors.
威尔姆斯瘤基因单核苷酸多态性（WT1 SNP）rs16754已被描述为急性髓系白血病患者的一个有利风险标志物。后续研究在成人和儿童患者中均得出了不一致的结果。我们首次分析了其对急性淋巴细胞白血病（ALL）患儿临床结局的影响。
采用等位基因鉴别法分析了1990年至2009年根据ALL柏林-法兰克福-明斯特治疗试验接受治疗的158例ALL患儿以及43例造血干细胞供者的WT1 SNP rs16754。比较SNP（WT1(GG/AG)）和野生型（WT1(AA)），分析WT1 SNP状态与疾病特征及临床结局的相关性。
23.4%的患者和34.9%的供者中发现至少一个次要等位基因（P = 0.07）。WT1(GG/AG)和WT1(AA)之间患者及疾病特征的分布相似。在多变量分析中，WT1 SNP是复发累积发生率（CIR；WT1(AA)与WT1(GG/AG)相比，HR = 3.384, P = 0.021）和无事件生存期（EFS；事件风险WT1(AA)与WT1(GG/AG)相比，HR = 2.503, P = 0.036）的独立良好预后标志物。对接受异基因造血干细胞移植的患者进行的单变量亚分析显示，CIR（P = 0.017）、EFS（P = 0.012）和总生存期（OS；P = 0.017）存在更显著差异。供者的WT1 SNP状态不影响结局。我们发现WT1 SNP与诊断时的WT1表达水平之间无相关性（P = 0.634）。
WT1 SNP rs16754预示着更好的CIR和EFS。移植患儿的结局差异更为显著。我们的研究结果表明WT1 SNP rs16754是小儿ALL中一个独立于已知风险因素的有利风险标志物。
