Enhanced Fructose Utilization Mediated by SLC2A5 Is a Unique Metabolic Feature of Acute Myeloid Leukemia with Therapeutic Potential

被引：184

作者：

Chen, Wen-Lian ^{[1
,2
,3
]}

Wang, Yue-Ying ^{[1
]}

Zhao, Aihua ^{[2
]}

Xia, Li ^{[1
]}

Xie, Guoxiang ^{[2
,3
]}

Su, Mingming ^{[2
,3
]}

Zhao, Linjing ^{[3
]}

Liu, Jiajian ^{[2
]}

Qu, Chun ^{[2
]}

Wei, Runmin ^{[3
]}

Rajani, Cynthia ^{[3
]}

Ni, Yan ^{[2
,3
]}

Cheng, Zhen ^{[4
,5
]}

Chen, Zhu ^{[1
]}

Chen, Sai-Juan ^{[1
]}

Jia, Wei ^{[2
,3
]}

机构：

[1] Shanghai Jiao Tong Univ, Sch Med, State Key Lab Med Genom, Dept Hematol,Shanghai Inst Hematol,Rui Jin Hosp, Shanghai 200025, Peoples R China

[2] Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Ctr Translat Med, Shanghai 200233, Peoples R China

[3] Univ Hawaii, Ctr Canc, Honolulu, HI 96813 USA

[4] Stanford Univ, Sch Med, Mol Imaging Program Stanford, Dept Radiol, Stanford, CA 94305 USA

[5] Stanford Univ, BioX Program, Canary Ctr Stanford Canc Early Detect, Stanford, CA 94305 USA

来源：

CANCER CELL | 2016年 / 30卷 / 05期

基金：

中国国家自然科学基金;

关键词：

EXPRESSION; TRANSPORTER; 2-DEOXY-D-GLUCOSE; SIGNATURE; SURVIVAL;

D O I：

10.1016/j.ccell.2016.09.006

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Rapidly proliferating leukemic progenitor cells consume substantial glucose, which 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 GLUTS, which compensates for glucose deficiency. Notably, AML patients with upregulated transcription of the GLUT5-encoding gene SLC2A5 or increased fructose utilization have poor outcomes. Pharmacological blockage of fructose uptake ameliorates leukemic phenotypes and potentiates the cytotoxicity of the antileukemic agent, Ara-C. In conclusion, this study highlights enhanced fructose utilization as a metabolic feature of AML and a potential therapeutic target.

引用

页码：779 / 791

页数：13

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