title: Enhanced Fructose Utilization Mediated by SLC2A5 Is a Unique Metabolic Feature of Acute Myeloid Leukemia with Therapeutic Potential.
abstract: 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 GLUT5, 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.
authors.affiliation: State Key Laboratory of Medical Genomics, Department of Hematology, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China; University of Hawaii Cancer Center, Honolulu, HI 96813, USA.
authors.forename: Wen-Lian
authors.initials: WL
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Medical Genomics, Department of Hematology, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Yue-Ying
authors.initials: YY
authors.lastname: Wang
authors.affiliation: Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Aihua
authors.initials: A
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Medical Genomics, Department of Hematology, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Li
authors.initials: L
authors.lastname: Xia
authors.affiliation: Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China; University of Hawaii Cancer Center, Honolulu, HI 96813, USA.
authors.forename: Guoxiang
authors.initials: G
authors.lastname: Xie
authors.affiliation: Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China; University of Hawaii Cancer Center, Honolulu, HI 96813, USA.
authors.forename: Mingming
authors.initials: M
authors.lastname: Su
authors.affiliation: University of Hawaii Cancer Center, Honolulu, HI 96813, USA.
authors.forename: Linjing
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Jiajian
authors.initials: J
authors.lastname: Liu
authors.affiliation: Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Qu
authors.affiliation: University of Hawaii Cancer Center, Honolulu, HI 96813, USA.
authors.forename: Runmin
authors.initials: R
authors.lastname: Wei
authors.affiliation: University of Hawaii Cancer Center, Honolulu, HI 96813, USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Rajani
authors.affiliation: Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China; University of Hawaii Cancer Center, Honolulu, HI 96813, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ni
authors.affiliation: Molecular Imaging Program at Stanford, Department of Radiology and Bio-X Program, Canary Center at Stanford for Cancer Early Detection, School of Medicine, Stanford University, Stanford, CA 94305, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: State Key Laboratory of Medical Genomics, Department of Hematology, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Medical Genomics, Department of Hematology, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: sjchen@stn.sh.cn.
authors.forename: Sai-Juan
authors.initials: SJ
authors.lastname: Chen
authors.affiliation: Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China; University of Hawaii Cancer Center, Honolulu, HI 96813, USA. Electronic address: wjia@cc.hawaii.edu.
authors.forename: Wei
authors.initials: W
authors.lastname: Jia
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003561:Cytarabine / Q000008:administration & dosage* / Q000494:pharmacology; D004357:Drug Synergism; D005632:Fructose / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques / Q000379:methods; D051296:Glucose Transporter Type 5 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008353:Mannitol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D011379:Prognosis; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D051296:Glucose Transporter Type 5; C495726:SLC2A5 protein, human; D003561:Cytarabine; D005632:Fructose; D008353:Mannitol; C031765:2,5-anhydromannitol
keywords: GLUT5; SLC2A5; acute myeloid leukemia; fructose utilization