ArticleNature2014
Contrasting roles of histone 3 lysine 27 demethylases in acute lymphoblastic leukaemia.
Erratum issuedOpen access · bronzeAbstract read
In one paragraph
Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 242 papers.
0numbers the graph read from it
0cells of the map it votes in
242citing papers in PubMed
42.7field-weighted citation impact, top 1% of its field
What it found
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Who cites it
242 citing papers in PubMed, 370 citations in OpenAlex.
- Trial
- A genomic and epigenomic lens into the biology of acute lymphoblastic leukaemia.Nature reviews. Cancer · 2026Review
- Loss of chromosome Y in hematopoietic cells: mechanisms and implications for human disease.MedScience · 2026Review
- UTY (KDM6C) in Cancer: Epigenetic Regulation, Tumour Suppressor Functions, and Clinical Implications.Epigenomes · 2026Review
- Intermittent myopic visual exposure triggers myopia progression via H3K27me3.Genome medicine · 2026Article
- PML::RARA-negative APL-mimicking AML with a novel KMT2C::CREB3L2 fusion and RARA/RXRA-mediated sensitivity to all-trans retinoic acid.Annals of hematology · 2026Article
- Structural landscape of H3K27me3 recognition by protein domains and their potential for inhibition.The Journal of biological chemistry · 2026Review
- GSK-J4 Suppresses Tumorigenesis by Targeting the PERK-c-Myc Pathway Through Endoplasmic Reticulum Stress Activation in Tuberous Sclerosis Complex.International journal of molecular sciences · 2026Article
- Iron: Regulation, redox homeostasis, and ferroptosis in cancer.Ferroptosis and oxidative stress · 2026Article
- KDM6 Demethylases Contribute to EWSR1::FLI1-Driven Oncogenic Reprogramming in Ewing Sarcoma.Cancer research · 2025Article
- Chromatin Regulatory Targets for Anticancer Therapeutics.Chemical reviews · 2025Review
- Structural mechanism of H3K27 demethylation and crosstalk with heterochromatin markers.Molecular cell · 2025Article
- JMJD3-mediated senescence is required to overcome stress-induced hematopoietic defects.EMBO reports · 2025Article
- HNRNPC and m6A RNA methylation control oncogenic transcription and metabolism in T-cell leukemia.Blood · 2025Article
- Glycolysis Induces Abnormal Transcription Through Histone Lactylation in T-cell Acute Lymphoblastic Leukemia.Genomics, proteomics & bioinformatics · 2025Article
- Harnessing the Deubiquitinase USP1 for Targeted Protein Stabilization.Journal of the American Chemical Society · 2025Article
- Targeted inhibition of WIP1 and histone H3K27 demethylase activity synergistically suppresses neuroblastoma growth.Cell death & disease · 2025Article
- Roles of Kdm6a and Kdm6b in Regulation of Mammalian Neural Regeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- 3D chromatin hubs as regulatory units of identity and survival in human acute leukemia.Molecular cell · 2025Article
- Sex differences in disease: sex chromosome and immunity.Journal of translational medicine · 2024Review
182 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
26 authors at 12 institutions in 5 countries.
Panagiotis Ntziachristos1] Howard Hughes Medical Institute and Department of Pathology, NYU School of Medicine, New York, New York 10016, USA [2] NYU Cancer Institute and Helen L. and Martin S. Kimmel Center for Stem Cell Biology, NYU School of Medicine, New York, New York 10016, USA [3].
Aristotelis Tsirigos1] Howard Hughes Medical Institute and Department of Pathology, NYU School of Medicine, New York, New York 10016, USA [2] Center for Health Informatics and Bioinformatics, NYU School of Medicine, New York, New York 10016, USA [3].
G Grant Welstead1] Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA [2] Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [3].
Thomas Trimarchi1] Howard Hughes Medical Institute and Department of Pathology, NYU School of Medicine, New York, New York 10016, USA [2] NYU Cancer Institute and Helen L. and Martin S. Kimmel Center for Stem Cell Biology, NYU School of Medicine, New York, New York 10016, USA.
Sofia Bakogianni1] Howard Hughes Medical Institute and Department of Pathology, NYU School of Medicine, New York, New York 10016, USA [2] NYU Cancer Institute and Helen L. and Martin S. Kimmel Center for Stem Cell Biology, NYU School of Medicine, New York, New York 10016, USA.
Luyao XuInstitute for Cancer Genetics, Columbia University Medical Center, New York, New York 10032, USA.
Evangelia Loizou1] Howard Hughes Medical Institute and Department of Pathology, NYU School of Medicine, New York, New York 10016, USA [2] NYU Cancer Institute and Helen L. and Martin S. Kimmel Center for Stem Cell Biology, NYU School of Medicine, New York, New York 10016, USA.
Linda HolmfeldtDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Alexandros Strikoudis1] Howard Hughes Medical Institute and Department of Pathology, NYU School of Medicine, New York, New York 10016, USA [2] NYU Cancer Institute and Helen L. and Martin S. Kimmel Center for Stem Cell Biology, NYU School of Medicine, New York, New York 10016, USA.
Bryan King1] Howard Hughes Medical Institute and Department of Pathology, NYU School of Medicine, New York, New York 10016, USA [2] NYU Cancer Institute and Helen L. and Martin S. Kimmel Center for Stem Cell Biology, NYU School of Medicine, New York, New York 10016, USA.
Jasper Mullenders1] Howard Hughes Medical Institute and Department of Pathology, NYU School of Medicine, New York, New York 10016, USA [2] NYU Cancer Institute and Helen L. and Martin S. Kimmel Center for Stem Cell Biology, NYU School of Medicine, New York, New York 10016, USA.
Jared BecksfortDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Jelena Nedjic1] Howard Hughes Medical Institute and Department of Pathology, NYU School of Medicine, New York, New York 10016, USA [2] NYU Cancer Institute and Helen L. and Martin S. Kimmel Center for Stem Cell Biology, NYU School of Medicine, New York, New York 10016, USA.
Elisabeth PaiettaMontefiore Medical Center North, Bronx, New York, New York 10467, USA.
Martin S TallmanMemorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
Jacob M Rowe1] Technion, Israel Institute of Technology, Haifa 31096, Israel [2] Shaare Zedek Medical Center, Jerusalem 9103102, Israel.
Giovanni TononFunctional Genomics of Cancer Unit, Division of Molecular Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, 20132 Milan, Italy.
Takashi Satoh1] Laboratory of Host Defense, WPI Immunology Frontier Research Center (WPI IFReC), Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan [2] Department of Host Defense, Research Institute for Microbial Diseases (RIMD), Osaka University, 3-1Yamada-oka, Suita, Osaka 565-0871, Japan.
Laurens KruidenierEpinova DPU, Immuno-Inflammation Therapy Area, GlaxoSmithKline R&D, Medicines Research Centre, GunnelsWood Road, Stevenage SG1 2NY, UK.
Rab PrinjhaEpinova DPU, Immuno-Inflammation Therapy Area, GlaxoSmithKline R&D, Medicines Research Centre, GunnelsWood Road, Stevenage SG1 2NY, UK.
Shizuo Akira1] Laboratory of Host Defense, WPI Immunology Frontier Research Center (WPI IFReC), Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan [2] Department of Host Defense, Research Institute for Microbial Diseases (RIMD), Osaka University, 3-1Yamada-oka, Suita, Osaka 565-0871, Japan.
Pieter Van Vlierberghe1] Institute for Cancer Genetics, Columbia University Medical Center, New York, New York 10032, USA [2] Center for Medical Genetics, Ghent University Hospital, 9000 Ghent, Belgium.
Adolfo A Ferrando1] Institute for Cancer Genetics, Columbia University Medical Center, New York, New York 10032, USA [2] Department of Pathology, Columbia University Medical Center, New York, New York 10032, USA [3] Department of Pediatrics, Columbia University Medical Center, New York, New York 10032, USA.
Rudolf Jaenisch1] Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA [2] Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Charles G MullighanDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Iannis Aifantis1] Howard Hughes Medical Institute and Department of Pathology, NYU School of Medicine, New York, New York 10016, USA [2] NYU Cancer Institute and Helen L. and Martin S. Kimmel Center for Stem Cell Biology, NYU School of Medicine, New York, New York 10016, USA.
Howard Hughes Medical Institute · USSt. Jude Children's Research Hospital · USCancer Genetics (United States) · USGlaxoSmithKline (United Kingdom) · GBOsaka University · JPColumbia University Irving Medical Center · USIstituti di Ricovero e Cura a Carattere Scientifico · ITMassachusetts Institute of Technology · USMemorial Sloan Kettering Cancer Center · USMontefiore Medical Center · USTechnion – Israel Institute of Technology · ILWhitehead Institute for Biomedical Research · US
Funding
Project-006U10CA180820 · NCI · ECOG-ACRIN MEDICAL RESEARCH FOUNDATION · PI Peter J ODwyer, MITCHELL D. SCHNALL · 2014 to 2026
$167.6MViral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI CHARLES ROBERTS · 1985 to 2026
$166.9MECOG OPERATIONS OFFICE (IBCSG)U10CA021115 · NCI · UNIVERSITY OF WISCONSIN MADISON · PI COMIS, ROBERT L · 1985 to 2013
$132.6MVIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI MATTHEW G. VANDER HEIDEN · 1985 to 2026
$93.9MVaccine FacilityP30CA016087 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ADRIANA HEGUY · 1985 to 2026
$83.1MTRAINING PROGRAM IN MOLECULAR ONCOLOGY &IMMUNOLOGYT32CA009161 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI CARROLL, WILLIAM L., LEVY, DAVID E · 1985 to 2020
$13.3MECOG Specimen BankingU24CA114737 · NCI · FRONTIER SCI &TECHNOLOGY RSCH FDN, INC · PI COMIS, ROBERT L · 2005 to 2014
$9.3MIn Vitro Reprogramming of Somatic Cells into Pluripotent ES-like CellsR37HD045022 · NICHD · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI JAENISCH, RUDOLF · 2009 to 2017
$7.5MRole 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
$6.3MThe role of the SCF/FBW7 ubiquitin ligase complex in hematopiesis and leukemia.R01CA133379 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI AIFANTIS, IANNIS · 2009 to 2018
$3.6MECOG-ACRIN INTEGRATED LEUKEMIA TRANSLATIONAL RESEARCH CENTERU10CA180827 · NCI · MONTEFIORE MEDICAL CENTER (BRONX, NY) · PI LEVINE, ROSS L, MELNICK, ARI M. · 2014 to 2018
$3.0MRegulation of hematopoietic stem cell differentiationR01CA105129 · NCI · UNIVERSITY OF CHICAGO · PI AIFANTIS, IANNIS · 2005 to 2014
$2.8MHoward Hughes Medical InstituteNCI NIH HHS 1R01CA105129NCI NIH HHS 1R01CA133379NCI NIH HHS 1R01CA149655NCI NIH HHS 5P30CA16087-31NCI NIH HHS 5R01CA169784NCI NIH HHS 5R01CA173636NCI NIH HHS 5 T32 CA009161-37NCI NIH HHS K99 CA188293NCI NIH HHS K99CA188293NCI NIH HHS P30 CA014051NCI NIH HHS P30 CA016087NCI NIH HHS P30 CA016087-30NCI NIH HHS P30 CA021765NCI NIH HHS R01 CA105129NCI NIH HHS R01 CA120196NCI NIH HHS R01CA120196NCI NIH HHS R01 CA133379NCI NIH HHS R01 CA149655NCI NIH HHS R01 CA169784NCI NIH HHS R01 CA173636NCI NIH HHS T32 CA009161NCI NIH HHS U10 CA021115NCI NIH HHS U10 CA180820NCI NIH HHS U10 CA180827NCI NIH HHS U10 CA21115NCI NIH HHS U24 CA114737NICHD NIH HHS R37-HD04502NICHD NIH HHS R37 HD045022
Abstract
T-cell acute lymphoblastic leukaemia (T-ALL) is a haematological malignancy with a dismal overall prognosis, including a relapse rate of up to 25%, mainly because of the lack of non-cytotoxic targeted therapy options. Drugs that target the function of key epigenetic factors have been approved in the context of haematopoietic disorders, and mutations that affect chromatin modulators in a variety of leukaemias have recently been identified; however, 'epigenetic' drugs are not currently used for T-ALL treatment. Recently, we described that the polycomb repressive complex 2 (PRC2) has a tumour-suppressor role in T-ALL. Here we delineated the role of the histone 3 lysine 27 (H3K27) demethylases JMJD3 and UTX in T-ALL. We show that JMJD3 is essential for the initiation and maintenance of T-ALL, as it controls important oncogenic gene targets by modulating H3K27 methylation. By contrast, we found that UTX functions as a tumour suppressor and is frequently genetically inactivated in T-ALL. Moreover, we demonstrated that the small molecule inhibitor GSKJ4 (ref. 5) affects T-ALL growth, by targeting JMJD3 activity. These findings show that two proteins with a similar enzymatic function can have opposing roles in the context of the same disease, paving the way for treating haematopoietic malignancies with a new category of epigenetic inhibitors.
Indexed as
AnimalsBenzazepinesEpigenesis, GeneticHistone DemethylasesHistonesJumonji Domain-Containing Histone DemethylasesLysineMethylationMicePrecursor Cell Lymphoblastic Leukemia-LymphomaPyrimidinesTumor Suppressor ProteinsBenzazepinesGSK-J4Histone DemethylasesHistonesJumonji Domain-Containing Histone DemethylasesKdm6b protein, mouseLysinePyrimidinesTumor Suppressor ProteinsUtx protein, mouse
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