State Key Laboratory of Medical Genomics, Institute of Health Sciences, Shanghai Institutes for Biological Sciences and Graduate School, Chinese Academy of Sciences and Shanghai Institute of Hematology, Rui Jin Hospital, affiliated to Shanghai Jiao Tong University School of Medicine , Shanghai, China.
J Proteome Res. 2013 Oct 4;12(10):4393-401. doi: 10.1021/pr400403p. Epub 2013 Sep 18.
Acute myeloid leukemia (AML) is a life-threatening hematological disease. Novel diagnostic and prognostic markers will be essential for new therapeutics and for significantly improving the disease prognosis. To characterize the metabolic features associated with AML and search for potential diagnostic and prognostic methods, here we analyzed the phenotypic characteristics of serum metabolite composition (metabonome) in a cohort of 183 patients with de novo acute myeloid leukemia together with 232 age- and gender-matched healthy controls using (1)H NMR spectroscopy in conjunction with multivariate data analysis. We observed significant serum metabonomic differences between AML patients and healthy controls and between AML patients with favorable and intermediate cytogenetic risks. Such differences were highlighted by systems differentiations in multiple metabolic pathways including glycolysis/gluconeogenesis, TCA cycle, biosynthesis of proteins and lipoproteins, and metabolism of fatty acids and cell membrane components, especially choline and its phosphorylated derivatives. This demonstrated the NMR-based metabonomics as a rapid and less invasive method for potential AML diagnosis and prognosis. The serum metabolic phenotypes observed here indicated that integration of metabonomics with other techniques will be useful for better understanding the biochemistry of pathogenesis and progression of leukemia.
急性髓系白血病(AML)是一种危及生命的血液系统疾病。新型诊断和预后标志物对于新的治疗方法以及显著改善疾病预后至关重要。为了描述与 AML 相关的代谢特征,并寻找潜在的诊断和预后方法,我们采用(1)H NMR 光谱结合多元数据分析,对 183 例初诊急性髓系白血病患者和 232 名年龄和性别匹配的健康对照者的血清代谢产物组成(代谢组)表型特征进行了分析。我们观察到 AML 患者与健康对照者之间,以及 AML 患者中具有良好和中等细胞遗传学风险者之间的血清代谢组存在显著差异。这些差异通过包括糖酵解/糖异生、三羧酸循环、蛋白质和脂蛋白的生物合成以及脂肪酸和细胞膜成分代谢在内的多种代谢途径中的系统差异得到强调,特别是胆碱及其磷酸化衍生物。这表明基于 NMR 的代谢组学是一种快速、微创的 AML 潜在诊断和预后方法。我们观察到的血清代谢表型表明,将代谢组学与其他技术相结合将有助于更好地理解白血病发病机制和进展的生物化学。