title: A distinct glucose metabolism signature of acute myeloid leukemia with prognostic value.
abstract: Acute myeloid leukemia (AML) is a group of hematological malignancies with high heterogeneity. There is an increasing need to improve the risk stratification of AML patients, including those with normal cytogenetics, using molecular biomarkers. Here, we report a metabolomics study that identified a distinct glucose metabolism signature with 400 AML patients and 446 healthy controls. The glucose metabolism signature comprises a panel of 6 serum metabolite markers, which demonstrated prognostic value in cytogenetically normal AML patients. We generated a prognosis risk score (PRS) with 6 metabolite markers for each patient using principal component analysis. A low PRS was able to predict patients with poor survival independently of well-established markers. We further compared the gene expression patterns of AML blast cells between low and high PRS groups, which correlated well to the metabolic pathways involving the 6 metabolite markers, with enhanced glycolysis and tricarboxylic [corrected] acid cycle at gene expression level in low PRS group. In vitro results demonstrated enhanced glycolysis contributed to decreased sensitivity to antileukemic agent arabinofuranosyl cytidine (Ara-C), whereas inhibition of glycolysis suppressed AML cell proliferation and potentiated cytotoxicity of Ara-C. Our study provides strong evidence for the use of serum metabolites and metabolic pathways as novel prognostic markers and potential therapeutic targets for AML.
authors.affiliation: Key Laboratory of Systems Biomedicine of Ministry of Education, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University (SJTU) and State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital, SJTU School of Medicine, Shanghai, China; Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China;
authors.forename: Wen-Lian
authors.initials: WL
authors.lastname: Chen
authors.affiliation: Key Laboratory of Systems Biomedicine of Ministry of Education, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University (SJTU) and State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital, SJTU School of Medicine, Shanghai, China;
authors.forename: Jing-Han
authors.initials: JH
authors.lastname: Wang
authors.affiliation: Key Laboratory of Systems Biomedicine of Ministry of Education, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University (SJTU) and State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital, SJTU School of Medicine, Shanghai, China; Center for Translational Medicine, Six People's Hospital, SJTU School of Medicine, Shanghai, China;
authors.forename: Ai-Hua
authors.initials: AH
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Systems Biomedicine of Ministry of Education, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University (SJTU) and State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital, SJTU School of Medicine, Shanghai, China;
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.affiliation: Key Laboratory of Systems Biomedicine of Ministry of Education, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University (SJTU) and State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital, SJTU School of Medicine, Shanghai, China; Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China;
authors.forename: Yi-Huang
authors.initials: YH
authors.lastname: Wang
authors.affiliation: Key Laboratory of Systems Biomedicine of Ministry of Education, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University (SJTU) and State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital, SJTU School of Medicine, Shanghai, China; Center for Translational Medicine, Six People's Hospital, SJTU School of Medicine, Shanghai, China;
authors.forename: Tian-Lu
authors.initials: TL
authors.lastname: Chen
authors.affiliation: Key Laboratory of Systems Biomedicine of Ministry of Education, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University (SJTU) and State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital, SJTU School of Medicine, Shanghai, China;
authors.forename: Jun-Min
authors.initials: JM
authors.lastname: Li
authors.affiliation: Key Laboratory of Systems Biomedicine of Ministry of Education, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University (SJTU) and State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital, SJTU School of Medicine, Shanghai, China;
authors.forename: Jian-Qing
authors.initials: JQ
authors.lastname: Mi
authors.affiliation: Key Laboratory of Systems Biomedicine of Ministry of Education, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University (SJTU) and State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital, SJTU School of Medicine, Shanghai, China;
authors.forename: Yong-Mei
authors.initials: YM
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Systems Biomedicine of Ministry of Education, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University (SJTU) and State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital, SJTU School of Medicine, Shanghai, China;
authors.forename: Yuan-Fang
authors.initials: YF
authors.lastname: Liu
authors.affiliation: Key Laboratory of Systems Biomedicine of Ministry of Education, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University (SJTU) and State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital, SJTU School of Medicine, Shanghai, China;
authors.forename: Yue-Ying
authors.initials: YY
authors.lastname: Wang
authors.affiliation: Zhejiang Institute of Hematology, and.
authors.forename: Jie
authors.initials: J
authors.lastname: Jin
authors.affiliation: Bone Marrow Transplantation Center, First Hospital, Zhejiang University School of Medicine, Hangzhou, China;
authors.forename: He
authors.initials: H
authors.lastname: Huang
authors.affiliation: Jiangsu Institute of Hematology, First Hospital, Soochow University School of Medicine, Suzhou, China;
authors.forename: De-Pei
authors.initials: DP
authors.lastname: Wu
authors.affiliation: Department of Hematology, First Hospital of China Medical University, Shenyang, China;
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Hematology, First Hospital of China Medical University, Shenyang, China;
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Yan
authors.affiliation: Department of Hematology, Second Hospital, Dalian Medical University, Dalian, China;
authors.forename: Jin-Song
authors.initials: JS
authors.lastname: Yan
authors.affiliation: Department of Hematology, First Hospital, Nanjing Medical University, Nanjing, China;
authors.forename: Jian-Yong
authors.initials: JY
authors.lastname: Li
authors.affiliation: Department of Hematology, First Hospital, Nanjing Medical University, Nanjing, China;
authors.forename: Shuai
authors.initials: S
authors.lastname: Wang
authors.affiliation: Institute of Hematology, Peking University and People's Hospital, Beijing, China;
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Huang
authors.affiliation: Department of Biostatistics, SJTU School of Medicine, Shanghai, China; and.
authors.forename: Bing-Shun
authors.initials: BS
authors.lastname: Wang
authors.affiliation: Key Laboratory of Systems Biomedicine of Ministry of Education, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University (SJTU) and State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital, SJTU School of Medicine, Shanghai, China; Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China;
authors.forename: Zhu
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Key Laboratory of Systems Biomedicine of Ministry of Education, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University (SJTU) and State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital, SJTU School of Medicine, Shanghai, China; Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China;
authors.forename: Sai-Juan
authors.initials: SJ
authors.lastname: Chen
authors.affiliation: Key Laboratory of Systems Biomedicine of Ministry of Education, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University (SJTU) and State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital, SJTU School of Medicine, Shanghai, China; Center for Translational Medicine, Six People's Hospital, SJTU School of Medicine, Shanghai, China; University of Hawaii Cancer Center, Honolulu, HI.
authors.forename: Wei
authors.initials: W
authors.lastname: Jia
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D005260:Female; D005947:Glucose / Q000378:metabolism*; D057809:HEK293 Cells; D018922:HL-60 Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D059467:Transcriptome; D020298:U937 Cells; D055815:Young Adult
chemical_list: D005947:Glucose