背景:早期研究确定急性髓性白血病(AML)细胞中某些脂质低于正常白细胞。因为现在已知脂质在细胞信号传导和稳态调节中起重要作用,经常在恶性肿瘤中受到干扰,我们对诊断时AML患者和健康献血者的血浆进行了全面的脂质组学调查.
方法:使用三个质谱平台在20名AML患者和20名健康献血者中测量血浆血脂谱。收集了总胆固醇和脂肪酸的数据,脂肪酸酰胺,甘油脂,磷脂,鞘脂,胆固醇酯,辅酶Q10和类二十烷酸。
结果:我们观察到血浆总脂肪酸和胆固醇的消耗,但是某些游离脂肪酸的增加和鞘脂的下降,磷酸胆碱,甘油三酯和胆固醇酯可能由AML细胞中脂肪酸氧化增强驱动。花生四烯酸和前体在AML中升高,特别是高骨髓(BM)或周围母细胞和不良预后风险的患者。PGF2α也升高,在低BM或外周母细胞和具有良好预后风险的患者中。AML血浆中广泛的脂质类别发生改变,指出了几种脂质代谢相互转化的紊乱,特别是与母细胞计数和预后风险有关。
结论:这些数据表明脂质在AML异质性和疾病结局中的潜在作用。
结论:几种脂质类型的分解代谢增强会增加预后风险,而血浆PGF2α可能是AML预后风险降低的标志物。
BACKGROUND: Early studies established that certain lipids were lower in acute myeloid leukemia (AML) cells than normal leukocytes. Because lipids are now known to play an important role in cell signaling and regulation of homeostasis, and are often perturbed in malignancies, we undertook a comprehensive lipidomic survey of plasma from AML patients at time of diagnosis and also healthy blood donors.
METHODS: Plasma lipid profiles were measured using three mass spectrometry platforms in 20 AML patients and 20 healthy blood donors. Data were collected on total cholesterol and fatty acids, fatty acid amides, glycerolipids, phospholipids, sphingolipids, cholesterol esters, coenzyme Q10 and eicosanoids.
RESULTS: We observed a depletion of plasma total fatty acids and cholesterol, but an increase in certain free fatty acids with the observed decline in sphingolipids, phosphocholines, triglycerides and cholesterol esters probably driven by enhanced fatty acid oxidation in AML cells. Arachidonic acid and precursors were elevated in AML, particularly in patients with high bone marrow (BM) or peripheral blasts and unfavorable prognostic risk. PGF2α was also elevated, in patients with low BM or peripheral blasts and with a favorable prognostic risk. A broad panoply of lipid classes is altered in AML plasma, pointing to disturbances of several lipid metabolic interconversions, in particular in relation to blast cell counts and prognostic risk.
CONCLUSIONS: These data indicate potential roles played by lipids in AML heterogeneity and disease outcome.
CONCLUSIONS: Enhanced catabolism of several lipid classes increases prognostic risk while plasma PGF2α may be a marker for reduced prognostic risk in AML.