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利用配对的临床骨髓血清样本对急性髓系白血病进展过程中的代谢谱进行分析。

Metabolic Profiling during Acute Myeloid Leukemia Progression Using Paired Clinical Bone Marrow Serum Samples.

作者信息

Kim Hyun Kyu, Son Su Young, Oh Jae Sang, Song Ye Na, Byun Ja Min, Koh Youngil, Hong Junshik, Yoon Sung-Soo, Lee Choong Hwan, Shin Dong-Yeop, Lee Man Ryul

机构信息

Soonchunhyang Institute of Medi-Bio Science (SIMS), Soon Chun Hyang University, Cheonan 31151, Korea.

Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Korea.

出版信息

Metabolites. 2021 Aug 31;11(9):586. doi: 10.3390/metabo11090586.

Abstract

Cellular metabolic changes reflect the characteristics of patients with acute myeloid leukemia (AML) caused by genetic variations, which are important in establishing AML treatment. However, little is known about the metabolic profile of patients with genetic variation-induced AML. Furthermore, the metabolites differ with disease progression. Here, metabolites in the bone marrow serum of ten patients with AML and healthy individuals were analyzed using gas chromatography-mass spectrometry. Compared with that in healthy individuals, expression of most metabolites decreased in patients with AML; hydroxylamine, 2-hydroxybutyric acid, monomethylphosphate, and ethylphosphate expression was unusually increased in the patients. We further examined serial metabolite changes across the initial diagnosis, postremission, and relapse phases. Patients with relapse showed increased metabolite expression compared with those in the diagnostic phase, confirming that patients with AML had aggressively modified leukemic cells. However, a clear difference in metabolite distribution was not observed between the diagnosis and complete remission phases, suggesting that the metabolic microenvironment did not change significantly despite complete remission. Interestingly, metabolite profiles differed with genetic variations in leukemic cells. Our results, which were obtained using paired samples collected during AML progression, provide valuable insights for identifying vulnerable targets in the AML metabolome and developing new treatment strategies.

摘要

细胞代谢变化反映了由基因变异引起的急性髓系白血病(AML)患者的特征,这对确立AML治疗方法很重要。然而,对于基因变异诱导的AML患者的代谢谱了解甚少。此外,代谢物会随疾病进展而有所不同。在此,使用气相色谱 - 质谱分析法对10例AML患者和健康个体骨髓血清中的代谢物进行了分析。与健康个体相比,AML患者中大多数代谢物的表达下降;而羟胺、2 - 羟基丁酸、单甲基磷酸酯和乙基磷酸酯的表达在患者中异常增加。我们进一步检查了初诊、缓解后和复发阶段的系列代谢物变化。与诊断阶段相比,复发患者的代谢物表达增加,证实AML患者具有活跃的白血病细胞修饰。然而,在诊断和完全缓解阶段之间未观察到代谢物分布的明显差异,这表明尽管完全缓解,代谢微环境并未显著改变。有趣的是,代谢物谱因白血病细胞中的基因变异而有所不同。我们使用在AML进展过程中收集的配对样本获得的结果,为识别AML代谢组中的脆弱靶点和制定新的治疗策略提供了有价值的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16f0/8471543/d57e7341b400/metabolites-11-00586-g001.jpg

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