Cancer-associated mutation and beyond: The emerging biology of isocitrate dehydrogenases in human disease

IDH3α regulates one-carbon metabolism in glioblastoma

(2019) Jasmine L. May et al.   Science Advances

R-2HG Exhibits Anti-tumor Activity by Targeting FTO/m 6 A/MYC/CEBPA Signaling

(2018) Rui Su et al.   CELL

Nestin-expressing progenitor cells: function, identity and therapeutic implications

(2018) Aurora Bernal et al.   CELLULAR AND MOLECULAR LIFE SCIENCES

Interfering peptides targeting protein–protein interactions: the next generation of drugs?

(2018) Heriberto Bruzzoni-Giovanelli et al.   DRUG DISCOVERY TODAY

JAK2/IDH-mutant–driven myeloproliferative neoplasm is sensitive to combined targeted inhibition

(2018) Anna Sophia McKenney et al.   JOURNAL OF CLINICAL INVESTIGATION

Suppression of antitumor T cell immunity by the oncometabolite (R)-2-hydroxyglutarate

(2018) Lukas Bunse et al.   NATURE MEDICINE

Modeling the diffusion of D-2-hydroxyglutarate from IDH1 mutant gliomas in the central nervous system

(2018) Andreas Linninger et al.   NEURO-ONCOLOGY

Durable Remissions with Ivosidenib in IDH1-Mutated Relapsed or Refractory AML

(2018) Courtney D. DiNardo et al.   NEW ENGLAND JOURNAL OF MEDICINE

Amazing Diversity in Biochemical Roles of Fe(II)/2-Oxoglutarate Oxygenases

(2018) Caitlyn Q Herr et al.   TRENDS IN BIOCHEMICAL SCIENCES

Pharmacodynamics of mutant-IDH1 inhibitors in glioma patients probed by in vivo 3D MRS imaging of 2-hydroxyglutarate

(2018) Ovidiu C. Andronesi et al.   Nature Communications

Metabolic Reprogramming in Amyotrophic Lateral Sclerosis

(2018) M. Szelechowski et al.   Scientific Reports

Mutant IDH1 Promotes Glioma Formation In Vivo

(2018) Beatrice Philip et al.   Cell Reports

The IDH1 Mutation-Induced Oncometabolite, 2-Hydroxyglutarate, May Affect DNA Methylation and Expression of PD-L1 in Gliomas

(2018) Luyan Mu et al.   Frontiers in Molecular Neuroscience

Crystal structures of pan-IDH inhibitor AG-881 in complex with mutant human IDH1 and IDH2

(2018) Rui Ma et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Transaminase Inhibition by 2-Hydroxyglutarate Impairs Glutamate Biosynthesis and Redox Homeostasis in Glioma

(2018) Samuel K. McBrayer et al.   CELL

Ivosidenib (IVO; AG-120) in mutant IDH1 relapsed/refractory acute myeloid leukemia (R/R AML): Results of a phase 1 study.

(2018) Daniel Aaron Pollyea et al.   JOURNAL OF CLINICAL ONCOLOGY

Acquired resistance to IDH inhibition through trans or cis dimer-interface mutations

(2018) Andrew M. Intlekofer et al.   NATURE

Genotype-targeted local therapy of glioma

(2018) Ganesh M. Shankar et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Molecular remission and response patterns in patients with mutant-IDH2 acute myeloid leukemia treated with enasidenib

(2018) Eytan M. Stein et al.   BLOOD

Isoform Switching as a Mechanism of Acquired Resistance to Mutant Isocitrate Dehydrogenase Inhibition

(2018) James J. Harding et al.   Cancer Discovery

Mutant IDH1 regulates the tumor-associated immune system in gliomas

(2017) Nduka M. Amankulor et al.   GENES & DEVELOPMENT

Isocitrate dehydrogenase mutations suppress STAT1 and CD8+ T cell accumulation in gliomas

(2017) Gary Kohanbash et al.   JOURNAL OF CLINICAL INVESTIGATION

BCAT1 restricts αKG levels in AML stem cells leading to IDHmut-like DNA hypermethylation

(2017) Simon Raffel et al.   NATURE

Homozygous mutation, p.Pro304His, in IDH3A, encoding isocitrate dehydrogenase subunit is associated with severe encephalopathy in infancy

(2017) Aviva Fattal-Valevski et al.   NEUROGENETICS

Whole-Exome Sequencing Identifies Biallelic IDH3A Variants as a Cause of Retinitis Pigmentosa Accompanied by Pseudocoloboma

(2017) Laurence H.M. Pierrache et al.   OPHTHALMOLOGY

Decoupling genetics, lineages, and microenvironment in IDH-mutant gliomas by single-cell RNA-seq

(2017) Andrew S. Venteicher et al.   SCIENCE

Discovery and Evaluation of Clinical Candidate IDH305, a Brain Penetrant Mutant IDH1 Inhibitor

(2017) Young Shin Cho et al.   ACS Medicinal Chemistry Letters

Systematic discovery of mutation-specific synthetic lethals by mining pan-cancer human primary tumor data

(2017) Subarna Sinha et al.   Nature Communications

Induction of synthetic lethality in IDH1-mutated gliomas through inhibition of Bcl-xL

(2017) Georg Karpel-Massler et al.   Nature Communications

AG-221, a First-in-Class Therapy Targeting Acute Myeloid Leukemia Harboring Oncogenic IDH2 Mutations

(2017) Katharine Yen et al.   Cancer Discovery

The Krebs Cycle Enzyme Isocitrate Dehydrogenase 3A Couples Mitochondrial Metabolism to Synaptic Transmission

(2017) Berrak Ugur et al.   Cell Reports

Cancer-Associated IDH1 Promotes Growth and Resistance to Targeted Therapies in the Absence of Mutation

(2017) Andrea E. Calvert et al.   Cell Reports

Low-Grade Astrocytoma Mutations in IDH1, P53, and ATRX Cooperate to Block Differentiation of Human Neural Stem Cells via Repression of SOX2

(2017) Aram S. Modrek et al.   Cell Reports

Editorial: The Metabolic-Inflammatory Axis in Brain Aging and Neurodegeneration

(2017) Fei Yin et al.   Frontiers in Aging Neuroscience

Isocitrate protects DJ-1 null dopaminergic cells from oxidative stress through NADP+-dependent isocitrate dehydrogenase (IDH)

(2017) Jinsung Yang et al.   PLoS Genetics

The β and γ subunits play distinct functional roles in the α2βγ heterotetramer of human NAD-dependent isocitrate dehydrogenase

(2017) Tengfei Ma et al.   Scientific Reports

Studies on the regulatory mechanism of isocitrate dehydrogenase 2 using acetylation mimics

(2017) Yuqun Xu et al.   Scientific Reports

Allosteric inhibitor remotely modulates the conformation of the orthestric pockets in mutant IDH2/R140Q

(2017) Jiao Chen et al.   Scientific Reports

A Brain Penetrant Mutant IDH1 Inhibitor Provides In Vivo Survival Benefit

(2017) Johnny Kopinja et al.   Scientific Reports

Mutant IDH1 Downregulates ATM and Alters DNA Repair and Sensitivity to DNA Damage Independent of TET2

(2016) Satoshi Inoue et al.   CANCER CELL

Expression of Idh1R132H in the Murine Subventricular Zone Stem Cell Niche Recapitulates Features of Early Gliomagenesis

(2016) Chiara Bardella et al.   CANCER CELL

Glioblastoma Therapy Can Be Augmented by Targeting IDH1-Mediated NADPH Biosynthesis

(2016) Daniel R. Wahl et al.   CANCER RESEARCH

IDH2 deficiency promotes mitochondrial dysfunction and dopaminergic neurotoxicity: implications for Parkinson’s disease

(2016) Hyunjin Kim et al.   FREE RADICAL RESEARCH

Wilms tumor 1 mutations in the pathogenesis of acute myeloid leukemia

(2016) R. Rampal et al.   HAEMATOLOGICA

Sterol Regulatory Element Binding Protein Regulates the Expression and Metabolic Functions of Wild-Type and OncogenicIDH1

(2016) Stéphane J. H. Ricoult et al.   MOLECULAR AND CELLULAR BIOLOGY

Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma

(2016) Itay Tirosh et al.   NATURE

IDH mutant gliomas escape natural killer cell immune surveillance by downregulation of NKG2D ligand expression

(2016) Xiaoran Zhang et al.   NEURO-ONCOLOGY

IDH1 deficiency attenuates gluconeogenesis in mouse liver by impairing amino acid utilization

(2016) Jing Ye et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Isocitrate Dehydrogenase Mutations Confer Dasatinib Hypersensitivity and SRC Dependence in Intrahepatic Cholangiocarcinoma

(2016) S. K. Saha et al.   Cancer Discovery

Wilms tumor 1 mutations in the pathogenesis of acute myeloid leukemia

(2016) R. Rampal et al.   HAEMATOLOGICA

Characteristics, clinical outcome, and prognostic significance of IDH mutations in AML

(2015) Courtney D. DiNardo et al.   AMERICAN JOURNAL OF HEMATOLOGY

Extreme Vulnerability of IDH1 Mutant Cancers to NAD+ Depletion

(2015) Kensuke Tateishi et al.   CANCER CELL

Adult Lineage-Restricted CNS Progenitors Specify Distinct Glioblastoma Subtypes

(2015) Sheila R. Alcantara Llaguno et al.   CANCER CELL

Idh1 protects murine hepatocytes from endotoxin-induced oxidative stress by regulating the intracellular NADP+/NADPH ratio

(2015) M Itsumi et al.   CELL DEATH AND DIFFERENTIATION

IDH2 deficiency promotes mitochondrial dysfunction and cardiac hypertrophy in mice

(2015) Hyeong Jun Ku et al.   FREE RADICAL BIOLOGY AND MEDICINE

Protein Hydroxylation Catalyzed by 2-Oxoglutarate-dependent Oxygenases

(2015) Suzana Markolovic et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

NADP+-IDH Mutations Promote Hypersuccinylation that Impairs Mitochondria Respiration and Induces Apoptosis Resistance

(2015) Feng Li et al.   MOLECULAR CELL

Insulator dysfunction and oncogene activation in IDH mutant gliomas

(2015) William A. Flavahan et al.   NATURE

New IDH1 mutant inhibitors for treatment of acute myeloid leukemia

(2015) Ujunwa C Okoye-Okafor et al.   Nature Chemical Biology

Integrated genomic characterization of IDH1-mutant glioma malignant progression

(2015) Hanwen Bai et al.   NATURE GENETICS

Isocitrate dehydrogenase 1 and 2 mutations induce BCL-2 dependence in acute myeloid leukemia

(2015) Steven M Chan et al.   NATURE MEDICINE

Oncometabolic mutation IDH1 R132H confers a metformin-hypersensitive phenotype

(2015) Elisabet Cuyàs et al.   Oncotarget

MiR-181a regulates lipid metabolism via IDH1

(2015) Bo Chu et al.   Scientific Reports

Oncometabolite D-2-Hydroxyglutarate Inhibits ALKBH DNA Repair Enzymes and Sensitizes IDH Mutant Cells to Alkylating Agents

(2015) Pu Wang et al.   Cell Reports

Metabolic Reprogramming of Cancer-Associated Fibroblasts by IDH3α Downregulation

(2015) Daoxiang Zhang et al.   Cell Reports

Mutant IDH1: An immunotherapeutic target in tumors

(2015) Theresa Schumacher et al.   OncoImmunology

Acetate Is a Bioenergetic Substrate for Human Glioblastoma and Brain Metastases

(2014) Tomoyuki Mashimo et al.   CELL

Proto-Oncogenic Role of Mutant IDH2 in Leukemia Initiation and Maintenance

(2014) Lev M. Kats et al.   Cell Stem Cell

Selective Inhibition of Mutant Isocitrate Dehydrogenase 1 (IDH1) via Disruption of a Metal Binding Network by an Allosteric Small Molecule

(2014) Gejing Deng et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Aberrant IDH3α expression promotes malignant tumor growth by inducing HIF-1-mediated metabolic reprogramming and angiogenesis

(2014) L Zeng et al.   ONCOGENE

Hominoid-specific enzyme GLUD2 promotes growth ofIDH1R132Hglioma

(2014) Ruihuan Chen et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Oxidation of Alpha-Ketoglutarate Is Required for Reductive Carboxylation in Cancer Cells with Mitochondrial Defects

(2014) Andrew R. Mullen et al.   Cell Reports

Serum 2-hydroxyglutarate levels predict isocitrate dehydrogenase mutations and clinical outcome in acute myeloid leukemia

(2013) C. D. DiNardo et al.   BLOOD

IDH1 and IDH2 Mutations in Gliomas

(2013) Adam L. Cohen et al.   Current Neurology and Neuroscience Reports

What a difference a hydroxyl makes: mutant IDH, (R)-2-hydroxyglutarate, and cancer

(2013) J.-A. Losman et al.   GENES & DEVELOPMENT

Prognostic significance of 2-hydroxyglutarate levels in acute myeloid leukemia in China

(2013) J.-H. Wang et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

IDH1 and IDH2 Mutations in Tumorigenesis: Mechanistic Insights and Clinical Perspectives

(2012) H. Yang et al.   CLINICAL CANCER RESEARCH

D-2-hydroxyglutarate produced by mutant IDH1 perturbs collagen maturation and basement membrane function

(2012) M. Sasaki et al.   GENES & DEVELOPMENT

Progress in understanding 2-hydroxyglutaric acidurias

(2012) Martijn Kranendijk et al.   JOURNAL OF INHERITED METABOLIC DISEASE

Adverse impact of IDH1 and IDH2 mutations in primary AML: Experience of the Spanish CETLAM group

(2012) J. Nomdedéu et al.   LEUKEMIA RESEARCH

IDH mutation impairs histone demethylation and results in a block to cell differentiation

(2012) Chao Lu et al.   NATURE

Transformation by the (R)-enantiomer of 2-hydroxyglutarate linked to EGLN activation

(2012) Peppi Koivunen et al.   NATURE

IDH1(R132H) mutation increases murine haematopoietic progenitors and alters epigenetics

(2012) Masato Sasaki et al.   NATURE

Overexpression of isocitrate dehydrogenase mutant proteins renders glioma cells more sensitive to radiation

(2012) Sichen Li et al.   NEURO-ONCOLOGY

Reverse TCA cycle flux through isocitrate dehydrogenases 1 and 2 is required for lipogenesis in hypoxic melanoma cells

(2012) Fabian V. Filipp et al.   Pigment Cell & Melanoma Research

Dysregulation of Glutathione Homeostasis in Neurodegenerative Diseases

(2012) William M. Johnson et al.   Nutrients

Tet2 Loss Leads to Increased Hematopoietic Stem Cell Self-Renewal and Myeloid Transformation

(2011) Kelly Moran-Crusio et al.   CANCER CELL

Mosaic Analysis with Double Markers Reveals Tumor Cell of Origin in Glioma

(2011) Chong Liu et al.   CELL

Hallmarks of Cancer: The Next Generation

(2011) Douglas Hanahan et al.   CELL

Evidence for Sequenced Molecular Evolution of IDH1 Mutant Glioblastoma From a Distinct Cell of Origin

(2011) Albert Lai et al.   JOURNAL OF CLINICAL ONCOLOGY

Ollier disease and Maffucci syndrome are caused by somatic mosaic mutations of IDH1 and IDH2

(2011) M Fernanda Amary et al.   NATURE GENETICS

Tet Proteins Can Convert 5-Methylcytosine to 5-Formylcytosine and 5-Carboxylcytosine

(2011) S. Ito et al.   SCIENCE

Leukemic IDH1 and IDH2 Mutations Result in a Hypermethylation Phenotype, Disrupt TET2 Function, and Impair Hematopoietic Differentiation

(2010) Maria E. Figueroa et al.   CANCER CELL

Inhibition of Glutaminase Preferentially Slows Growth of Glioma Cells with Mutant IDH1

(2010) M. J. Seltzer et al.   CANCER RESEARCH

Sirt3 Mediates Reduction of Oxidative Damage and Prevention of Age-Related Hearing Loss under Caloric Restriction

(2010) Shinichi Someya et al.   CELL

Molecular mechanisms of “off-on switch” of activities of human IDH1 by tumor-associated mutation R132H

(2010) Bei Yang et al.   CELL RESEARCH

IDH2 Mutations in Patients with D-2-Hydroxyglutaric Aciduria

(2010) M. Kranendijk et al.   SCIENCE

Selective acquisition of IDH1 R132C mutations in astrocytomas associated with Li-Fraumeni syndrome

(2009) Takuya Watanabe et al.   ACTA NEUROPATHOLOGICA

Cancer-associated IDH1 mutations produce 2-hydroxyglutarate

(2009) Lenny Dang et al.   NATURE

IDH1andIDH2Mutations in Gliomas

(2009) Hai Yan et al.   NEW ENGLAND JOURNAL OF MEDICINE

Erasing the methyl mark: histone demethylases at the center of cellular differentiation and disease

(2008) P. A.C. Cloos et al.   GENES & DEVELOPMENT

Novel suppressors of α-synuclein toxicity identified using yeast

(2008) Jun Liang et al.   HUMAN MOLECULAR GENETICS

Cytoplasmic Serine Hydroxymethyltransferase Regulates the Metabolic Partitioning of Methylenetetrahydrofolate but Is Not Essential in Mice

(2008) Amanda J. MacFarlane et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Insights from retinitis pigmentosa into the roles of isocitrate dehydrogenases in the Krebs cycle

(2008) Dyonne T Hartong et al.   NATURE GENETICS