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血清代谢组学鉴定儿童急性淋巴细胞白血病的生物标志物及通路分析。

Biomarker identification and pathway analysis by serum metabolomics of childhood acute lymphoblastic leukemia.

机构信息

Department of Pediatrics, The 2nd Affiliated Hospital of Harbin Medical University, Xuefu Road 246, Nangang District, Harbin 150001, China.

Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Baojian Road 157, Nangang District, Harbin 150081, China.

出版信息

Clin Chim Acta. 2014 Sep 25;436:207-16. doi: 10.1016/j.cca.2014.05.022. Epub 2014 Jun 5.

DOI:10.1016/j.cca.2014.05.022
PMID:24909874
Abstract

BACKGROUND

Acute lymphoblastic leukemia (ALL) is a common hematological malignant neoplasm that typically affects children. Although intense chemotherapeutic regimens have been useful to combat the disease, approximately 20% of patients will relapse despite treatment. Diagnosing ALL requires bone marrow puncture procedure, which many parents do not consent to for it is invasive. Additionally, metabolic alterations associated with the disease are unclear.

METHODS

Metabolic alterations associated with ALL were investigated by performing serum metabolomics based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry and multivariate statistical analysis. Ingenuity Pathways Analysis (IPA) was also performed.

RESULTS

Thirty metabolites (17 detected in positive mode and 13 in negative mode) were differentially expressed between patients with ALL and control patients; these metabolites were selected as potential biomarkers. Based on IPA analysis, glycerophospholipid metabolism is deregulated in patients with ALL and may represent an underlying metabolic pathway associated with disease progression.

CONCLUSIONS

Metabolomics can be used to analyze the metabolic activity of ALL patients compared to healthy controls. The data we provide here suggest that glycerophospholipid metabolism may be a key mechanism underlying disease progression and development.

摘要

背景

急性淋巴细胞白血病(ALL)是一种常见的血液恶性肿瘤,通常发生在儿童身上。尽管强化化疗方案对治疗该病非常有效,但仍有约 20%的患者在治疗后复发。ALL 的诊断需要骨髓穿刺,这对许多父母来说是不可接受的,因为它具有侵入性。此外,与疾病相关的代谢改变尚不清楚。

方法

采用超高效液相色谱-四极杆飞行时间串联质谱联用和多元统计分析方法进行血清代谢组学研究,探讨 ALL 相关的代谢改变。同时还进行了 IPA 分析。

结果

ALL 患者与对照组患者之间有 30 种代谢物(正离子模式下检测到 17 种,负离子模式下检测到 13 种)存在差异表达;这些代谢物被选为潜在的生物标志物。基于 IPA 分析,甘油磷脂代谢在 ALL 患者中失调,可能代表与疾病进展相关的潜在代谢途径。

结论

代谢组学可用于分析 ALL 患者与健康对照者的代谢活性。我们提供的数据表明,甘油磷脂代谢可能是疾病进展和发展的关键机制。

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