Metabolomic Profiling and Bioanalysis of Chronic Myeloid Leukemia: Identifying Biomarkers for Treatment Response and Disease Monitoring.

IF 3.4 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Metabolites Pub Date : 2025-06-06 DOI:10.3390/metabo15060376
Selim Sayın, Murat Yıldırım, Batuhan Erdoğdu, Ozan Kaplan, Emine Koç, Tuba Bulduk, Melda Cömert, Mustafa Güney, Mustafa Çelebier, Meltem Aylı
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引用次数: 0

Abstract

Background: Including Chronic Myeloid Leukemia (CML) patients with deep molecular responses (MR4.5) and those with suboptimal responses provides valuable insights into treatment-associated metabolic changes. This study aimed to characterize the metabolomic alterations associated with CML and identify potential biomarkers for treatment response, particularly in patients achieving a deeper molecular response versus those with poorer responses.

Methods: Plasma samples were collected from 51 chronic-phase CML patients and 24 healthy controls. CML patients were classified into two groups based on molecular responses: T1 (BCR-ABL1 IS ≤ 0.0032%) and T2 (BCR-ABL1 IS > 0.0032%, <1%). Metabolomic profiling was conducted using quadrupole time-of-flight liquid chromatography/mass spectrometry. The data analysis involved a partial least squares discriminant analysis, variable importance in projection (VIP) scores, and a pathway enrichment analysis. Significant metabolites were identified.

Results: The PLS-DA revealed distinct metabolomic profiles between CML patients and healthy controls as well as between the T1 and T2 groups. Key differentiating metabolites with VIP scores > 1.5 included glutamate, hypoxanthine, and D-galactonic acid. In the T2 group, significant increases in malate and 5-aminoimidazole-4-carboxamide ribonucleotide were observed, reflecting disruptions in purine metabolism, the tricarboxylic acid cycle, and amino acid metabolism. The pathway enrichment analysis highlighted significant alterations in CML energy metabolism, nucleotide synthesis, and amino acid biosynthesis.

Conclusions: CML patients exhibit pronounced metabolic changes, particularly in energy and nucleotide metabolism, which are linked to treatment response. These findings provide novel insights into CML biology and suggest potential biomarkers for monitoring treatment efficacy and predicting outcomes and therapeutic targets for improving treatment outcomes and overcoming tyrosine kinase inhibitor resistance.

慢性髓性白血病的代谢组学分析和生物分析:确定治疗反应和疾病监测的生物标志物。
背景:纳入具有深度分子反应(MR4.5)和次优反应的慢性髓性白血病(CML)患者为治疗相关代谢变化提供了有价值的见解。本研究旨在表征与CML相关的代谢组学改变,并确定治疗反应的潜在生物标志物,特别是在获得较深分子反应的患者与较差反应的患者中。方法:采集51例慢性粒细胞白血病患者和24例健康对照者的血浆标本。根据分子反应将CML患者分为T1组(BCR-ABL1 IS≤0.0032%)和T2组(BCR-ABL1 IS > 0.0032%)。结果:PLS-DA显示CML患者与健康对照组之间以及T1组与T2组之间存在不同的代谢组学特征。VIP评分> 1.5的关键代谢物包括谷氨酸、次黄嘌呤和d -半乳糖醛酸。在T2组中,观察到苹果酸和5-氨基咪唑-4-羧胺核糖核苷酸的显著增加,反映了嘌呤代谢、三羧酸循环和氨基酸代谢的中断。通路富集分析强调了CML能量代谢、核苷酸合成和氨基酸生物合成的显著变化。结论:CML患者表现出明显的代谢变化,特别是能量和核苷酸代谢,这与治疗反应有关。这些发现为CML生物学提供了新的见解,并提出了监测治疗疗效、预测治疗结果和治疗靶点的潜在生物标志物,以改善治疗结果和克服酪氨酸激酶抑制剂耐药性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Metabolites
Metabolites Biochemistry, Genetics and Molecular Biology-Molecular Biology
CiteScore
5.70
自引率
7.30%
发文量
1070
审稿时长
17.17 days
期刊介绍: Metabolites (ISSN 2218-1989) is an international, peer-reviewed open access journal of metabolism and metabolomics. Metabolites publishes original research articles and review articles in all molecular aspects of metabolism relevant to the fields of metabolomics, metabolic biochemistry, computational and systems biology, biotechnology and medicine, with a particular focus on the biological roles of metabolites and small molecule biomarkers. Metabolites encourages scientists to publish their experimental and theoretical results in as much detail as possible. Therefore, there is no restriction on article length. Sufficient experimental details must be provided to enable the results to be accurately reproduced. Electronic material representing additional figures, materials and methods explanation, or supporting results and evidence can be submitted with the main manuscript as supplementary material.
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