Enhanced Fructose Utilization Mediated by SLC2A5 Is a Unique Metabolic Feature of Acute Myeloid Leukemia with Therapeutic Potential.
Enhanced Fructose Utilization Mediated by SLC2A5 Is a Unique Metabolic Feature of Acute Myeloid Leukemia with Therapeutic Potential.
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DOI：
10.1016/j.ccell.2016.09.006
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发表时间：
2016-11-14
期刊：
影响因子：
50.3
通讯作者：
Jia W
中科院分区：
文献类型：
--
作者：
Chen WL;Wang YY;Zhao A;Xia L;Xie G;Su M;Zhao L;Liu J;Qu C;Wei R;Rajani C;Ni Y;Cheng Z;Chen Z;Chen SJ;Jia W
快速增殖的白血病祖细胞消耗大量的葡萄糖，这可能导致骨髓中葡萄糖不足。我们发现，急性髓性白血病（AML）细胞倾向于果糖利用与上调果糖转运蛋白GLUT 5，弥补葡萄糖缺乏。值得注意的是，GLUT 5编码基因SLC 2A 5转录上调或果糖利用增加的AML患者预后较差。果糖摄取的药理学阻断可改善白血病表型并增强抗白血病药物Ara-C的细胞毒性。总之，这项研究强调了果糖利用率的提高作为AML的代谢特征和潜在的治疗靶点。Chen等人表明，AML细胞在低葡萄糖条件下通过上调果糖转运蛋白GLUT 5表现出增强的果糖利用，从而加剧白血病表型。果糖利用的药理学阻断选择性地消除AML细胞并增强Ara-C的功效。
Rapidly proliferating leukemic progenitor cells consume substantial glucose that may lead to glucose insufficiency in bone marrow. We show that acute myeloid leukemia (AML) cells are prone to fructose utilization with an upregulated fructose transporter GLUT5, compensating for glucose deficiency. Notably, AML patients with upregulated transcription of GLUT5-encoding gene SLC2A5 or increased fructose utilization have poor outcomes. Pharmacological blockage of fructose uptake ameliorates leukemic phenotypes and potentiates the cytotoxicity of antileukemic agent, Ara-C. In conclusion, this study highlights enhanced fructose utilization as a metabolic feature of AML and a potential therapeutic target. Chen et al. show that AML cells exhibit enhanced fructose utilization under low-glucose conditions via upregulating the fructose transporter GLUT5, exacerbating leukemic phenotypes. Pharmacologic blockade of fructose utilization selectively eliminates AML cells and enhances the efficacy of Ara-C.