ArticleMolecular cell2021
R-2-hydroxyglutarate attenuates aerobic glycolysis in leukemia by targeting the FTO/m
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Article in Molecular cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 213 papers, 1 of them a synthesis that pooled it.
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213citing papers in PubMed, 1 pooled it
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Who cites it
213 citing papers in PubMed, 1 synthesis or guideline pooled it, 336 citations in OpenAlex.
- Emerging Role of Epitranscriptomics in Diabetes Mellitus and Its Complications.Frontiers in endocrinology · 2022Pooled it
- The role, regulatory mechanisms, and therapeutic implications of FTO in gastrointestinal cancer.Genes & diseases · 2026Review
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- ENO1 promotes acute myeloid leukemia progression through SCD1-mediated lipid metabolism reprogramming.Blood advances · 2026Article
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- RNA modifications in cancer: regulators of tumor evolution and therapeutic response.Molecular cancer · 2026Review
- A targetable FTO/SLC7A11/CBS/CTH axis controls cysteine metabolism, growth and survival in NSCLC.Science advances · 2026Article
- Article
- LDLRAD2 drives glycolysis and angiogenesis to promote extramedullary infiltration in acute myeloid leukemia.iScience · 2026Article
- Review
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- Epigenetic transcriptional regulation of skeletal aging: The emerging role of mJournal of orthopaedic translation · 2026Review
- Suppression of Tumor Aggression Through Metabolic Reprogramming via Oxamate Targeting LDHA.International journal of molecular sciences · 2026Review
- Absolute dynamic and relative static: the relationship of glycolysis and OXPHOS in cancer development.Cell death discovery · 2026Review
- NNature reviews. Cancer · 2026Review
- The AHCY-adenosine complex rewires mRNA methylation to enhance fatty acid biosynthesis and tumorigenesis.Cell research · 2026Article
- Risk factors for early mortality (within 6 weeks of diagnosis) in Chinese children with acute leukemia: a single-center retrospective cohort study.Annals of hematology · 2026Article
- Lactylation in cancer: molecular mechanisms and advances in clinical study.Molecular cancer · 2026Review
- The Regulatory Role of mCells · 2026Review
- Epitranscriptomic control of cancer hallmarks: Functions, mechanisms, and therapeutics of RNA modifications.Cancer cell · 2026Review
153 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
29 authors at 7 institutions in 2 countries.
Ying QingDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA; Irell and Manella Graduate School of Biological Sciences, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.
Lei DongDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.
Lei GaoDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA; Department of Pathology and Genomic Medicine, Houston Methodist, Houston, TX 77030, USA.
Chenying LiDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA; Key Laboratory of Hematopoietic Malignancies, The First Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang 31003, China.
Yangchan LiDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA; Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
Li HanDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA; School of Pharmacy, China Medical University, Shenyang, Liaoning 110001, China.
Emily PrinceDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.
Brandon TanDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.
Xiaolan DengDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.
Collin WetzelDepartment of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45219, USA.
Chao ShenDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.
Min GaoDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA; School of Pharmaceutical Science and Technology, Tianjin Key Laboratory for Modern Drug Delivery and High Efficiency, and Collaborative Innovation Center of Chemical Science and Engineer (Tianjin), Tianjin University, Tianjin 300072, China.
Zhenhua ChenDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.
Wei LiDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.
Bin ZhangDepartment of Hematologic Malignancies Translational Science, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA; City of Hope Comprehensive Cancer Center, City of Hope, Duarte, CA 91010, USA; Gehr Family Center for Leukemia Research, City of Hope, Duarte, CA 91010, USA.
Daniel BraasUCLA Metabolomics Center, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Johanna Ten HoeveUCLA Metabolomics Center, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Gerardo Javier SanchezUCLA Metabolomics Center, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Huiying ChenDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.
Lai N ChanDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA; Department of Internal Medicine (Hematology) and Center of Molecular and Cellular Oncology, Yale Cancer Center, Yale School of Medicine, New Haven, CT 06511, USA.
Chun-Wei ChenDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA; City of Hope Comprehensive Cancer Center, City of Hope, Duarte, CA 91010, USA.
David AnnIrell and Manella Graduate School of Biological Sciences, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA; Department of Diabetes Complications and Metabolism, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA; City of Hope Comprehensive Cancer Center, City of Hope, Duarte, CA 91010, USA.
Lei JiangMolecular and Cellular Endocrinology, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA; City of Hope Comprehensive Cancer Center, City of Hope, Duarte, CA 91010, USA.
Markus MüschenDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA; City of Hope Comprehensive Cancer Center, City of Hope, Duarte, CA 91010, USA; Department of Internal Medicine (Hematology) and Center of Molecular and Cellular Oncology, Yale Cancer Center, Yale School of Medicine, New Haven, CT 06511, USA.
Guido MarcucciDepartment of Hematologic Malignancies Translational Science, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA; City of Hope Comprehensive Cancer Center, City of Hope, Duarte, CA 91010, USA; Gehr Family Center for Leukemia Research, City of Hope, Duarte, CA 91010, USA.
David R PlasDepartment of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45219, USA.
Zejuan LiDepartment of Pathology and Genomic Medicine, Houston Methodist, Houston, TX 77030, USA.
Rui SuDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA. Electronic address: rsu@coh.org.
Jianjun ChenDepartment of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA; City of Hope Comprehensive Cancer Center, City of Hope, Duarte, CA 91010, USA; Gehr Family Center for Leukemia Research, City of Hope, Duarte, CA 91010, USA. Electronic address: jianchen@coh.org.
City of Hope · USUniversity of California, Los Angeles · USHouston Methodist · USUniversity of Cincinnati Medical Center · USYale Cancer Center · USSun Yat-sen University · CNTianjin University · CN
Funding
Transgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI STANLEY R. HAMILTON · 1985 to 2026
$86.3MMetabolic gatekeepers in B-cell malignanciesR35CA197628 · NCI · YALE UNIVERSITY · PI Markus Müschen · 2016 to 2026
$11.7MTargeted activation of autoimmune checkpoints in B cell malignanciesR01CA157644 · NCI · YALE UNIVERSITY · PI Markus Müschen · 2011 to 2026
$5.7MECOG-ACRIN INTEGRATED LEUKEMIA TRANSLATIONAL RESEARCH CENTERU10CA180827 · NCI · MONTEFIORE MEDICAL CENTER (BRONX, NY) · PI LEVINE, ROSS L, MELNICK, ARI M. · 2014 to 2018
$3.0MTargeting FTO to treat acute myeloid leukemiaR01CA243386 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI CHEN, JIANJUN · 2020 to 2024
$2.8MPRE-B CELL RECEPTOR SIGNALING IN ACUTE LYMPHOBLASTIC LEUKEMIAR01CA137060 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MÜSCHEN, MARKUS · 2009 to 2016
$2.7MThe role and mechanism of METTL3/METTL14-mediated RNA modification in the pathogenesis and drug-resistance of AMLR01CA236399 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI CHEN, JIANJUN · 2019 to 2023
$2.3MTargeting TET1 signaling to treat acute myeloid leukemiaR01CA211614 · NCI · UNIVERSITY OF CINCINNATI · PI CHEN, JIANJUN · 2017 to 2021
$2.3MThe function and underlying mechanism of TET1 in myelodysplastic syndromesR01DK124116 · NIDDK · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI CHEN, JIANJUN · 2020 to 2023
$2.2MThe role and mechanism of FTO in leukemogenesis and drug responseR01CA214965 · NCI · UNIVERSITY OF CINCINNATI · PI CHEN, JIANJUN · 2017 to 2021
$2.1MDNA Damage Response and Oncogenic SignalingT32CA186895 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI BINGHUI SHEN, Jeremy Michael Stark · 2016 to 2026
$2.1MCD25-mediated feedback control of BCR-signaling and its oncogenic mimicsR01CA213138 · NCI · YALE UNIVERSITY · PI MÜSCHEN, MARKUS · 2017 to 2022
$1.9MHoward Hughes Medical InstituteNCI NIH HHS R01 CA137060NCI NIH HHS R01 CA157644NCI NIH HHS R01 CA169458NCI NIH HHS R01 CA172558NCI NIH HHS R01 CA211614NCI NIH HHS R01 CA213138NCI NIH HHS R01 CA214965NCI NIH HHS R01 CA236399NCI NIH HHS R01 CA243386NCI NIH HHS R35 CA197628NCI NIH HHS T32 CA186895NCI NIH HHS U10 CA180827NIDDK NIH HHS R01 DK124116
Abstract
R-2-hydroxyglutarate (R-2HG), a metabolite produced by mutant isocitrate dehydrogenases (IDHs), was recently reported to exhibit anti-tumor activity. However, its effect on cancer metabolism remains largely elusive. Here we show that R-2HG effectively attenuates aerobic glycolysis, a hallmark of cancer metabolism, in (R-2HG-sensitive) leukemia cells. Mechanistically, R-2HG abrogates fat-mass- and obesity-associated protein (FTO)/N
Indexed as
Alpha-Ketoglutarate-Dependent Dioxygenase FTOAnimalsAntineoplastic AgentsCell Line, TumorCell ProliferationFemaleFluorouracilGene Expression Regulation, NeoplasticGlutaratesGlycolysisHEK293 CellsHumansK562 CellsLactate DehydrogenasesLeukemia, Myeloid, AcuteMalealpha-hydroxyglutarateAlpha-Ketoglutarate-Dependent Dioxygenase FTOAntineoplastic AgentsD-lactate dehydrogenaseFluorouracilFTO protein, humanGlutaratesLactate DehydrogenasesPFKP protein, humanPhosphofructokinase-1, Type CRNA-Binding ProteinsRNA, Small InterferingYTHDF2 protein, humancancer metabolismFTOglycolysisLDHBleukemiaN(6)-methyladenosine (m(6)A) modificationPFKPR-2HGRNA stabilityYTHDF2
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