The use of mass spectrometry for protein identification and quantification in cerebrospinal fluid (CSF) is at the forefront of research efforts to identify and explore biomarkers for the early diagnosis and prognosis of neurologic disorders. Here we implemented a 4-plex N,N-dimethyl leucine (DiLeu) isobaric labeling strategy in a longitudinal study aiming to investigate protein dynamics in children with B-cell acute lymphoblastic leukemia (B-cell ALL) undergoing chemotherapy. The temporal profile of CSF proteome during chemotherapy treatment at weeks 5, 10–14, and 24–28 highlighted many differentially expressed proteins, such as neural cell adhesion molecule, neuronal growth regulator 1, and secretogranin-3, all of which play important roles in neurodegenerative diseases. A total of 63 proteins were significantly altered across all of the time points investigated. The most over-represented biological processes from gene ontology analysis included platelet degranulation, complement activation, cell adhesion, fibrinolysis, neuron projection, regeneration, and regulation of neuron death. We expect that results from this and future studies will provide a means to monitor neurotoxicity and develop strategies to prevent central nervous system injury in response to chemotherapy in children.

中文翻译：

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利用 4-Plex N,N-二甲基亮氨酸 (DiLeu) 标签的同量异位标记策略揭示了 B 细胞急性淋巴细胞白血病儿童脑脊液化疗引起的蛋白质组变化。

使用质谱法对脑脊液 (CSF) 中的蛋白质进行识别和定量是识别和探索用于神经系统疾病早期诊断和预后的生物标志物的研究工作的前沿。在这里，我们在一项纵向研究中实施了 4 重N , N-二甲基亮氨酸 (DiLeu) 同量异位标记策略，旨在研究接受化疗的 B 细胞急性淋巴细胞白血病 (B 细胞 ALL) 儿童的蛋白质动态。化疗期间第 5、10-14 和 24-28 周脑脊液蛋白质组的时间分布突出显示了许多差异表达的蛋白质，例如神经细胞粘附分子、神经元生长调节剂 1 和促分泌素 3，所有这些蛋白质都发挥着重要作用在神经退行性疾病中。在所有研究的时间点上，共有 63 种蛋白质发生了显着改变。基因本体分析中最常见的生物过程包括血小板脱颗粒、补体激活、细胞粘附、纤维蛋白溶解、神经元投射、再生和神经元死亡调节。我们期望这项研究和未来研究的结果将提供一种监测神经毒性的方法，并制定预防儿童化疗引起的中枢神经系统损伤的策略。