Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA 94720, USA.
Division of Biostatistics, School of Public Health, University of California, Berkeley, CA 94720, USA.
Leuk Res. 2020 Jan;88:106268. doi: 10.1016/j.leukres.2019.106268. Epub 2019 Nov 6.
The developing fetus is exposed to chemicals, which are metabolized to electrophiles that form adducts with nucleophilic Cys34 of human serum albumin (HSA). By measuring these adducts in neonatal blood spots (NBS), we obtain information regarding fetal exposures during the last month of gestation. To discover potential risk factors for childhood leukemia resulting from in utero exposures, we used untargeted adductomics to measure HSA-Cys34 adducts in 782 archived NBS, collected from incident cases of childhood acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) and matched population-based controls. Among a total of 28 Cys34 modifications that were measured, we found no differences in adduct abundances between childhood leukemia cases and controls overall. However, cases of T-cell ALL had higher abundances of adducts of reactive carbonyl species and a Cys34 disulfide of homocysteine was present at lower levels in AML cases. These results suggest that oxidative stress and lipid peroxidation may be etiologic factors of T-cell ALL, and alterations in one-carbon metabolism and epigenetic changes may be predictors of AML. Future replication of the results with larger sample sizes is necessary.
发育中的胎儿会接触到化学物质，这些物质会被代谢为亲电试剂，与人体血清白蛋白 (HSA) 的亲核 Cys34 形成加合物。通过测量新生儿血斑 (NBS) 中的这些加合物，我们可以获得妊娠最后一个月胎儿暴露的信息。为了发现与宫内暴露相关的儿童白血病的潜在风险因素，我们使用非靶向加合物组学方法测量了 782 份存档的 NBS 中 HSA-Cys34 加合物，这些 NBS 是从儿童急性淋巴细胞白血病 (ALL) 或急性髓系白血病 (AML) 的新发病例和基于人群的匹配对照组中收集的。在所测量的总共 28 种 Cys34 修饰中，我们没有发现儿童白血病病例和对照组之间加合物丰度的总体差异。然而，T 细胞 ALL 病例中反应性羰基物种的加合物丰度较高，而 AML 病例中同型半胱氨酸的 Cys34 二硫键水平较低。这些结果表明，氧化应激和脂质过氧化可能是 T 细胞 ALL 的病因因素，而一碳代谢和表观遗传变化的改变可能是 AML 的预测因素。未来需要更大的样本量进行结果复制。
