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急性淋巴细胞白血病患儿血清脂质组学和代谢组学特征的液相色谱-质谱分析

LC-MS analysis of serum lipidomic and metabolomic signatures in pediatric patients with acute lymphoblastic leukemia.

作者信息

Yan Feiyu, Wang Shengnan, Wang Yilin, Sun Yan, Yang Jing, Sun Lirong, Zaytseva Yekaterina Y, Deng Pan, Wang Lingzhen

机构信息

Department of Pediatrics Hematology and Oncology, The Affiliated Hospital of Qingdao University, Shandong, 266003, Shandong, China.

Department of Pharmaceutical Analysis, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China.

出版信息

Ital J Pediatr. 2025 Mar 12;51(1):74. doi: 10.1186/s13052-025-01921-z.

Abstract

BACKGROUND

Acute lymphoblastic leukemia (ALL) is a prevalent hematologic malignancy that primarily affects children. The diagnosis and treatment of pediatric ALL remain challenging. This study aimed to identify differential lipids and metabolites that may hold potential for improving ALL treatment.

METHODS

In this retrospective case-control study, serum samples obtained from children with ALL and healthy controls were analyzed. Serum lipidome and metabolome alterations of ALL were analyzed by comparing pediatric patients with ALL with healthy controls based on liquid chromatography high-resolution mass spectrometry analysis of serum lipidomic and metabolomic signatures.

RESULTS

We identified 2,298 lipid features in the serum. Among them, 72 (3.13%) differed significantly in pediatric patients with ALL compared to healthy controls. Notably, sphingolipids (ceramide and sphingomyelin) and phospholipids exhibited the most pronounced changes. Targeted analysis of ceramides revealed significantly elevated levels of Cer 18:0 and Cer 20:0 in the serum of pediatric patients with ALL. Additionally, gut microbial-related lipids (such as sulfonolipids and fatty acid esters of hydroxy fatty acids) showed significant alterations. Metabolomic analysis identified 15 differential metabolites, indicating disrupted nucleotide and amino acid metabolism. Furthermore, the dysregulated lipids and metabolites correlated with various blood indicators, with ceramide and nucleosides positively associated with white blood cell count but negatively correlated with hemoglobin and platelet.

CONCLUSION

These findings shed light on abnormal molecular signatures contributing to pediatric ALL and may serve as potential biomarker panel for therapy of ALL.

摘要

背景

急性淋巴细胞白血病(ALL)是一种常见的血液系统恶性肿瘤,主要影响儿童。小儿ALL的诊断和治疗仍然具有挑战性。本研究旨在识别可能有助于改善ALL治疗的差异脂质和代谢物。

方法

在这项回顾性病例对照研究中,分析了从ALL患儿和健康对照者获得的血清样本。基于血清脂质组学和代谢组学特征的液相色谱高分辨率质谱分析,通过比较ALL患儿与健康对照者,分析ALL的血清脂质组和代谢组改变。

结果

我们在血清中鉴定出2298种脂质特征。其中,与健康对照相比,ALL患儿中有72种(3.13%)存在显著差异。值得注意的是,鞘脂(神经酰胺和鞘磷脂)和磷脂表现出最明显的变化。对神经酰胺的靶向分析显示,ALL患儿血清中Cer 18:0和Cer 20:0水平显著升高。此外,肠道微生物相关脂质(如磺脂和羟基脂肪酸的脂肪酸酯)也有显著改变。代谢组学分析鉴定出15种差异代谢物,表明核苷酸和氨基酸代谢紊乱。此外,脂质和代谢物的失调与各种血液指标相关,神经酰胺和核苷与白细胞计数呈正相关,但与血红蛋白和血小板呈负相关。

结论

这些发现揭示了导致小儿ALL的异常分子特征,并可能作为ALL治疗的潜在生物标志物组。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aaf1/11905700/a91763ea9e8c/13052_2025_1921_Fig1_HTML.jpg

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