Petrick Lauren, Imani Partow, Perttula Kelsi, Yano Yukiko, Whitehead Todd, Metayer Catherine, Schiffman Courtney, Dolios Georgia, Dudoit Sandrine, Rappaport Stephen
The Institute of Exposomics Research, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA; Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA; Center for Integrative Research on Childhood Leukemia and the Environment, University of California, Berkeley, CA, 94720, USA.
Division of Biostatistics, School of Public Health, University of California, Berkeley, CA, 94720, USA.
Leuk Res. 2021 Jul;106:106585. doi: 10.1016/j.leukres.2021.106585. Epub 2021 Apr 24.
The etiology of pediatric acute myeloid leukemia (AML) is largely unknown, but evidence for mutations in utero and long latency periods suggests that environmental factors play a role. Therefore, we used untargeted metabolomics of archived newborn dried blood spots (DBS) to investigate neonatal exposures as potential causal risk factors for AML. Untargeted metabolomics profiling was performed on DBS punches from 48 pediatric patients with AML and 46 healthy controls as part of the California Childhood Leukemia Study (CCLS). Because sex disparities are suggested by differences in AML incidence rates, metabolite features associated with AML were identified in analyses stratified by sex. There was no overlap between the 16 predictors of AML in females and 15 predictors in males, suggesting that neonatal metabolomic profiles of pediatric AML risk are sex-specific. In females, four predictors of AML were putatively annotated as ceramides, a class of metabolites that has been linked with cancer cell proliferation. In females, two metabolite predictors of AML were strongly correlated with breastfeeding duration, indicating a possible biological link between this putative protective risk factor and childhood leukemia. In males, a heterogeneous metabolite profile of AML predictors was observed. Replication with larger participant numbers is required to validate findings.
小儿急性髓系白血病（AML）的病因在很大程度上尚不清楚，但子宫内突变和较长潜伏期的证据表明环境因素起了作用。因此，我们利用存档的新生儿干血斑（DBS）进行非靶向代谢组学研究，以探究新生儿暴露作为AML潜在因果风险因素的情况。作为加利福尼亚儿童白血病研究（CCLS）的一部分，对48例小儿AML患者和46例健康对照的DBS样本进行了非靶向代谢组学分析。由于AML发病率的差异提示了性别差异，因此在按性别分层的分析中确定了与AML相关的代谢物特征。女性AML的16个预测因子与男性的15个预测因子之间没有重叠，这表明小儿AML风险的新生儿代谢组学特征具有性别特异性。在女性中，4个AML预测因子被推测为神经酰胺，这是一类与癌细胞增殖有关的代谢物。在女性中，2个AML代谢物预测因子与母乳喂养持续时间密切相关，表明这种假定的保护风险因素与儿童白血病之间可能存在生物学联系。在男性中，观察到AML预测因子的代谢物谱具有异质性。需要更大样本量的重复研究来验证这些发现。
