ArticleCell reports2014
DNA hydroxymethylation profiling reveals that WT1 mutations result in loss of TET2 function in acute myeloid leukemia.
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Article in Cell reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 171 papers.
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171citing papers in PubMed
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Who cites it
171 citing papers in PubMed, 260 citations in OpenAlex.
- Genomic landscape of patients with FLT3-mutated acute myeloid leukemia (AML) treated within the CALGB 10603/RATIFY trial.Leukemia · 2022Trial
- The prognostic impact of CEBPA mutation in acute myeloid leukemia patients undergoing allogeneic hematopoietic stem cell transplantation.Bone marrow transplantation · 2026Article
- TET2 loss triggers ssDNA gap accumulation and heightened PARP inhibitor sensitivity.Nature communications · 2026Article
- DNA Methylation Stochasticity Is Linked to Transcriptional Variability and Convergent Epigenetic Disruption across Genetic Subtypes of Acute Myeloid Leukemia.Cancer research · 2026Article
- Synergistic intragenic epigenetic deregulation by IDH2 and SRSF2 mutations causes mis-splicing of key transcriptional regulators.Science advances · 2026Article
- Differentiation therapy in acute myeloid leukaemia: molecular basis, clinical progress, and future perspectives.Frontiers in medicine · 2026Review
- The role of epigenetic modifications in hematological cancers.Frontiers in oncology · 2026Review
- TET knockout cells transit between pluripotent states and exhibit precocious germline entry.The EMBO journal · 2025Article
- Analysis and Interpretation of Somatic NMD-Escaping Variants in Oncogenes and Dual-Function Genes across Adult and Pediatric Cancer Cohorts.medRxiv : the preprint server for health sciences · 2025Article
- Retinoic acid and ascorbate synergize to suppress myeloid leukemia via TET2 activation.Cell reports · 2025Article
- Ten-Eleven Translocation Family Proteins: Structure, Biological Functions, Diseases, and Targeted Therapy.MedComm · 2025Review
- Emergence of CpG-cluster blanket methylation in aged tissues: a novel signature of epigenomic aging.Nucleic acids research · 2025Article
- Additional Sex Combs-like Family Associated with Epigenetic Regulation.International journal of molecular sciences · 2024Review
- Associations in cell type-specific hydroxymethylation and transcriptional alterations of pediatric central nervous system tumors.Nature communications · 2024Article
- The Killer's Web: Interconnection between Inflammation, Epigenetics and Nutrition in Cancer.International journal of molecular sciences · 2024Review
- Micronutrient regulation of the DNA methylome.Frontiers in epigenetics and epigenomics · 2024Review
- Myelodysplasia after clonal hematopoiesis with APOBEC3-mediated CYBB inactivation in retroviral gene therapy for X-CGD.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- TET2 lesions enhance the aggressiveness of CEBPA-mutant acute myeloid leukemia by rebalancing GATA2 expression.Nature communications · 2023Article
- Perturbed epigenetic transcriptional regulation in AML with IDH mutations causes increased susceptibility to NK cells.Leukemia · 2023Article
- TET (Ten-eleven translocation) family proteins: structure, biological functions and applications.Signal transduction and targeted therapy · 2023Review
111 more citing papers are in PubMed but not listed here.
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Authors and funding
34 authors at 12 institutions in 3 countries.
Raajit RampalHuman Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA; Leukemia Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Altuna AlkalinDepartment of Physiology and Biophysics, Weill Cornell Medical College, New York, NY 10065, USA; Berlin Institute for Medical Systems Biology, Max Delbrück Centre for Molecular Medicine, Robert-Rössle-Straße 10, 13125 Berlin, Germany.
Jozef MadzoSection of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
Aparna VasanthakumarSection of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
Elodie PronierHuman Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Jay PatelHuman Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Yushan LiDepartment of Hematology/Oncology, Weill Cornell Medical College, New York, NY 10065, USA.
Jihae AhnHuman Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Omar Abdel-WahabHuman Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA; Leukemia Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Alan ShihHuman Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA; Leukemia Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Chao LuCancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Patrick S WardCancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Jennifer J TsaiDepartment of Immunology and Microbial Pathogenesis, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA.
Todd HricikHuman Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Valeria ToselloInstitute for Cancer Genetics, Columbia University Medical Center, New York, NY 10032, USA.
Jacob E TallmanHuman Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Xinyang ZhaoMolecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Danette DanielsPromega Corporation, Madison, WI 53703, USA.
Qing DaiDepartment of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA.
Luisa CiminioDepartment of Pathology, New York University Cancer Institute, New York, NY 10016, USA.
Iannis AifantisDepartment of Pathology, New York University Cancer Institute, New York, NY 10016, USA.
Chuan HeDepartment of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA.
Francois FuksLaboratory of Cancer Epigenetics, Faculty of Medicine, Université Libre de Bruxelles, 1070 Brussels, Belgium.
Martin S TallmanLeukemia Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Adolfo FerrandoInstitute for Cancer Genetics, Columbia University Medical Center, New York, NY 10032, USA.
Stephen NimerDepartment of Medicine, Sylvester Comprehensive Cancer Center, Miami, FL 33136, USA.
Elisabeth PaiettaMontefiore Medical Center, New York, NY 10466, USA.
Craig B ThompsonCancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Jonathan D LichtRobert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL 60611, USA.
Christopher E MasonDepartment of Physiology and Biophysics, Weill Cornell Medical College, New York, NY 10065, USA; The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA; The Feil Family Brain and Mind Research Institute, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA. Electronic address: chm2042@med.cornell.edu.
Lucy A GodleySection of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA; The University of Chicago Comprehensive Cancer Research Center, Chicago, IL 60637, USA. Electronic address: lgodley@medicine.bsd.uchicago.edu.
Ari MelnickDepartment of Hematology/Oncology, Weill Cornell Medical College, New York, NY 10065, USA. Electronic address: amm2014@med.cornell.edu.
Maria E FigueroaDepartment of Hematology/Oncology, Weill Cornell Medical College, New York, NY 10065, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: marfigue@med.umich.edu.
Ross L LevineHuman Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA; Leukemia Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. Electronic address: leviner@mskcc.org.
Memorial Sloan Kettering Cancer Center · USUniversity of Chicago · USCornell University · USCancer Genetics (United States) · USNew York University · USMax Delbrück Center · DEMIND Research Institute · USMontefiore Medical Center · USNorthwestern University · USPromega (United States) · USSylvester Comprehensive Cancer Center · USUniversité Libre de Bruxelles · BE
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4MProject-006U10CA180820 · NCI · ECOG-ACRIN MEDICAL RESEARCH FOUNDATION · PI Peter J ODwyer, MITCHELL D. SCHNALL · 2014 to 2026
$167.6MTumor Environment and Metastasis (TEAM) Research ProgramP30CA060553 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Daniela E Matei · 1993 to 2026
$153.9MECOG OPERATIONS OFFICE (IBCSG)U10CA021115 · NCI · UNIVERSITY OF WISCONSIN MADISON · PI COMIS, ROBERT L · 1985 to 2013
$132.6MRe-Engineering Translational Research at the University of ChicagoUL1TR000430 · NCATS · UNIVERSITY OF CHICAGO · PI SOLWAY, JULIAN · 2012 to 2016
$20.2MThe Cell-Of-Origin of Human CancersU54CA143798 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI MICHOR, FRANZISKA · 2009 to 2014
$11.2MECOG Specimen BankingU24CA114737 · NCI · FRONTIER SCI &TECHNOLOGY RSCH FDN, INC · PI COMIS, ROBERT L · 2005 to 2014
$9.3MRole of TET2 mutations in malignant transformation and acute myeloid leukemiaR01CA173636 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI AIFANTIS, IANNIS, LEVINE, ROSS L · 2013 to 2022
$6.3MEpigenome Interactions in Complex Neurogenetic DisordersR01NS076465 · NINDS · WEILL MEDICAL COLL OF CORNELL UNIV · PI MASON, CHRISTOPHER EDWARD, ROSS, MARGARET ELIZABETH · 2011 to 2015
$5.8MTargeting p300 and lysine acetylation in AMLR01CA166835 · NCI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI Stephen D. Nimer · 2012 to 2026
$4.6MECOG-ACRIN INTEGRATED LEUKEMIA TRANSLATIONAL RESEARCH CENTERU10CA180827 · NCI · MONTEFIORE MEDICAL CENTER (BRONX, NY) · PI LEVINE, ROSS L, MELNICK, ARI M. · 2014 to 2018
$3.0MRole of IDH Mutations in Acute Myeloid MalignanciesR01CA168802 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI THOMPSON, CRAIG B · 2013 to 2017
$1.8MHoward Hughes Medical InstituteNCATS NIH HHS UL1 TR000430NCI NIH HHS CA129831NCI NIH HHS CA129831-03S1NCI NIH HHS CA172636-01NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA060553NCI NIH HHS R01 CA129831NCI NIH HHS R01 CA166835NCI NIH HHS R01 CA168802NCI NIH HHS R01 CA169784NCI NIH HHS R01 CA173636NCI NIH HHS R21 CA176362NCI NIH HHS U10 CA021115NCI NIH HHS U10 CA180820NCI NIH HHS U10 CA180827NCI NIH HHS U24 CA114737NCI NIH HHS U54 CA143798NCI NIH HHS U54CA143798-01NHGRI NIH HHS K01 HG006699NHGRI NIH HHS R01 HG006798NHGRI NIH HHS R01HG006798NINDS NIH HHS 01NS076465NINDS NIH HHS R01 NS076465
Abstract
Somatic mutations in IDH1/IDH2 and TET2 result in impaired TET2-mediated conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). The observation that WT1 inactivating mutations anticorrelate with TET2/IDH1/IDH2 mutations in acute myeloid leukemia (AML) led us to hypothesize that WT1 mutations may impact TET2 function. WT1 mutant AML patients have reduced 5hmC levels similar to TET2/IDH1/IDH2 mutant AML. These mutations are characterized by convergent, site-specific alterations in DNA hydroxymethylation, which drive differential gene expression more than alterations in DNA promoter methylation. WT1 overexpression increases global levels of 5hmC, and WT1 silencing reduced 5hmC levels. WT1 physically interacts with TET2 and TET3, and WT1 loss of function results in a similar hematopoietic differentiation phenotype as observed with TET2 deficiency. These data provide a role for WT1 in regulating DNA hydroxymethylation and suggest that TET2 IDH1/IDH2 and WT1 mutations define an AML subtype defined by dysregulated DNA hydroxymethylation.
Indexed as
Gene Expression Regulation, Neoplastic5-MethylcytosineAnimalsCell DifferentiationCytosineDioxygenasesDNA-Binding ProteinsEnhancer Elements, GeneticHematopoiesisHumansLeukemia, Myeloid, AcuteMice, KnockoutMutationPromoter Regions, GeneticProtein BindingProto-Oncogene Proteins5-hydroxymethylcytosine5-MethylcytosineCytosineDioxygenasesDNA-Binding ProteinsProto-Oncogene ProteinsTET2 protein, humanWT1 protein, humanWT1 Proteins
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