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

被引：174

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

共 34 条

[21] Prognostic Relevance of Integrated Genetic Profiling in Acute Myeloid Leukemia
Patel, Jay P.
Goenen, Mithat
Figueroa, Maria E.
Fernandez, Hugo
Sun, Zhuoxin
Racevskis, Janis
Van Vlierberghe, Pieter
Dolgalev, Igor
Thomas, Sabrena
Aminova, Olga
Huberman, Kety
Cheng, Janice
Viale, Agnes
Socci, Nicholas D.
Heguy, Adriana
Cherry, Athena
Vance, Gail
Higgins, Rodney R.
Ketterling, Rhett P.
Gallagher, Robert E.
Litzow, Mark
van den Brink, Marcel R. M.
Lazarus, Hillard M.
Rowe, Jacob M.
Luger, Selina
Ferrando, Adolfo
Paietta, Elisabeth
Tallman, Martin S.
Melnick, Ari
Abdel-Wahab, Omar
Levine, Ross L.
[J]. NEW ENGLAND JOURNAL OF MEDICINE, 2012, 366 (12) : 1079 - 1089
[22] Efficient and rapid induction of a chronic myelogenous leukemia-like myeloproliferative disease in mice receiving P210 bcr/abl-transduced bone marrow
Pear, WS
Miller, JP
Xu, LW
Pui, JC
Soffer, B
Quackenbush, RC
Pendergast, AM
Bronson, R
Aster, JC
Scott, ML
Baltimore, D
[J]. BLOOD, 1998, 92 (10) : 3780 - 3792
[23] A phase I dose-escalation trial of 2-deoxy-D-glucose alone or combined with docetaxel in patients with advanced solid tumors
Raez, Luis E.
Papadopoulos, Kyriakos
Ricart, Alejandro D.
Chiorean, E. Gabriella
DiPaola, Robert S.
Stein, Mark N.
Lima, Caio M. Rocha
Schlesselman, James J.
Tolba, Khaled
Langmuir, Virginia K.
Kroll, Stewart
Jung, Donald T.
Kurtoglu, Metin
Rosenblatt, Joseph
Lampidis, Theodore J.
[J]. CANCER CHEMOTHERAPY AND PHARMACOLOGY, 2013, 71 (02) : 523 - 530
[24] Identification of genes with abnormal expression changes in acute myeloid leukemia
Stirewalt, Derek L.
Meshinchi, Soheil
Kopecky, Kenneth J.
Fan, Wenhong
Pogosova-Agadjanyan, Era L.
Engel, Julia H.
Cronk, Michelle R.
Dorcy, Kathleen Shannon
McQuary, Amy R.
Hockenbery, David
Wood, Brent
Heimfeld, Shelly
Radich, Jerald P.
[J]. GENES CHROMOSOMES & CANCER, 2008, 47 (01) : 8 - 20
[25] Advances in understanding the leukaemia microenvironment
Tabe, Yoko
Konopleva, Marina
[J]. BRITISH JOURNAL OF HAEMATOLOGY, 2014, 164 (06) : 767 - 778
[26] Metabolomics of the Tumor Microenvironment in Pediatric Acute Lymphoblastic Leukemia
Tiziani, Stefano
Kang, Yunyi
Harjanto, Ricky
Axelrod, Joshua
Piermarocchi, Carlo
Roberts, William
Paternostro, Giovanni
[J]. PLOS ONE, 2013, 8 (12):
[27] Prognostically useful gene-expression profiles in acute myeloid leukemia
Valk, PJM
Verhaak, RGW
Beijen, MA
Erpelinck, CAJ
van Doorn-Khosrovani, SBV
Boer, JM
Beverloo, HB
Moorhouse, MJ
van der Spek, PJ
Löwenberg, B
Delwel, R
[J]. NEW ENGLAND JOURNAL OF MEDICINE, 2004, 350 (16) : 1617 - 1628
[28] Vijayaraghavan R, 2006, BIOMED ENVIRON SCI, V19, P96
[29] Prognostic significance of 2-hydroxyglutarate levels in acute myeloid leukemia in China
Wang, Jiang-Han
Chen, Wen-Lian
Li, Jun-Min
Wu, Song-Fang
Chen, Tian-Lu
Zhu, Yong-Mei
Zhang, Wei-Na
Li, Yang
Qiu, Yun-Ping
Zhao, Ai-Hua
Mi, Jian-Qing
Jin, Jie
Wang, Yun-Gui
Ma, Qiu-Ling
Huang, He
Wu, De-Pei
Wang, Qin-Rong
Li, Yan
Yan, Xiao-Jing
Yan, Jin-Song
Li, Jian-Yong
Wang, Shuai
Huang, Xiao-Jun
Wang, Bing-Shun
Jia, Wei
Shen, Yang
Chen, Zhu
Chen, Sai-Juan
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2013, 110 (42) : 17017 - 17022
[30] C-KIT mutation cooperates with full-length AML1-ETO to induce acute myeloid leukemia in mice
Wang, Yue-Ying
Zhao, Li-Juan
Wu, Chuan-Feng
Liu, Ping
Shi, Lin
Liang, Yang
Xiong, Shu-Min
Mi, Jian-Qing
Chen, Zhu
Ren, Ruibao
Chen, Sai-Juan
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (06) : 2450 - 2455

← 1 2 3 4 →