INTRODUCTION Acute myeloid leukemia (AML) is characterized by a set of malignant proliferations leading to an accumulation of blasts in the bone marrow and blood. The prognosis is pejorative due to the molecular complexity and pathways implicated in leukemogenesis. OBJECTIVES Our research was focused on comparing the metabolic profiles of leukemic cells in basal culture and deprivation conditions to investigate their behaviors under metabolic stress. METHODS We performed untargeted metabolomics using 1H HRMAS-NMR. Five human leukemic cell lines-KG1, K562, HEL, HL60 and OCIAML3-were studied in the basal and nutrient deprivation states. A multivariate analysis of the metabolic profile was performed to find over- or under- expressed metabolites in the different cell lines, depending on the experimental conditions. RESULTS In the basal state, each leukemic cell line exhibited a specific metabolic signature related to the diversity of AML subtypes represented and their phenotypes. When cultured in a serum-free medium, they showed quick metabolic adaptation and continued to proliferate and survive despite the lack of nutrients. Low apoptosis was observed. Increased phosphocholine and glutathione was a common feature of all the observed cell lines, with the maximum increase in these metabolites at 24 h of culture, suggesting the involvement of lipid metabolism and oxidative stress regulators in the survival mechanism developed by the leukemic cells. CONCLUSIONS Our study provides new insights into the metabolic mechanisms in leukemogenesis and suggests a hierarchy of metabolic pathways activated within leukemic cells, some dependent on their genotypes and others conserved among the subtypes but commonly induced under micro-environmental stress.

中文翻译：

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白血病细胞中代谢途径的差异激活取决于其基因型和微环境压力。

引言急性髓细胞性白血病（AML）的特征是一系列恶性增生，导致骨髓和血液中的母细胞积聚。由于分子的复杂性和与白血病发生有关的途径，因此预后较差。目的我们的研究集中在比较基础培养和剥夺条件下白血病细胞的代谢特征，以研究其在代谢应激下的行为。方法我们使用1 H HRMAS-NMR进行了非靶向代谢组学。研究了五种人类白血病细胞系KG1，K562，HEL，HL60和OCIAML3的基础和营养剥夺状态。根据实验条件，对代谢谱进行了多变量分析，以发现不同细胞系中过度表达或表达不足的代谢产物。结果在基础状态下，每种白血病细胞系均表现出与所代表的AML亚型及其表型的多样性有关的特定代谢特征。当在无血清培养基中培养时，尽管缺乏营养，它们仍显示出快速的代谢适应性，并继续增殖和存活。观察到低凋亡。磷酸胆碱和谷胱甘肽的增加是所有观察到的细胞系的共同特征，这些代谢物在培养24小时后最大增加，表明脂质代谢和氧化应激调节剂参与白血病细胞形成的存活机制。结论我们的研究为白血病发生中的代谢机制提供了新见解，并提出了白血病细胞内激活的代谢途径的层次结构，