ArticleNature communications2015
ZEB2 drives immature T-cell lymphoblastic leukaemia development via enhanced tumour-initiating potential and IL-7 receptor signalling.
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Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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59 citing papers in PubMed, 87 citations in OpenAlex.
- Trial
- ID2 secures cDC1 specification by antagonizing E proteins at a pleiotropic Zeb2 enhancer.Nature immunology · 2026Article
- The Interleukin-7 Receptor Signaling Pathway and Its Perturbation in Immunodeficiency, Autoimmune Disease and Lymphoid Malignancy.Biomolecules · 2026Review
- The transcription factor ZEB2 mediates the antitumor efficacy of tumor-infiltrating lymphocytes in non-small cell lung cancer.Cell death & disease · 2025Article
- Transcriptomic characterisation of acute myeloid leukemia cell lines bearing the same t(9;11) driver mutation reveals different molecular signatures.BMC genomics · 2025Article
- Decoding the Implications of Zinc in the Development and Therapy of Leukemia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Review
- The Role of Epithelial-to-Mesenchymal Transition Transcription Factors (EMT-TFs) in Acute Myeloid Leukemia Progression.Biomedicines · 2024Review
- Acute lymphoblastic leukaemia.Nature reviews. Disease primers · 2024Review
- Epithelial-Mesenchymal Transition in Acute Leukemias.International journal of molecular sciences · 2024Review
- The epithelial-mesenchymal plasticity landscape: principles of design and mechanisms of regulation.Nature reviews. Genetics · 2023Review
- Stromal-induced epithelial-mesenchymal transition induces targetable drug resistance in acute lymphoblastic leukemia.Cell reports · 2023Article
- Resistance to the BCL-XL degrader DT2216 in T-cell acute lymphoblastic leukemia is rare and correlates with decreased BCL-XL proteolysis.Cancer chemotherapy and pharmacology · 2023Article
- An "unexpected" role for EMT transcription factors in hematological development and malignancy.Frontiers in immunology · 2023Review
- JAK/BCL2 inhibition acts synergistically with LSD1 inhibitors to selectively target ETP-ALL.Leukemia · 2022Article
- Either IL-7 activation of JAK-STAT or BEZ inhibition of PI3K-AKT-mTOR pathways dominates the single-cell phosphosignature ofHaematologica · 2022Article
- Article
- Myb drives B-cell neoplasms and myeloid malignancies in vivo.Blood advances · 2022Article
- Inside the biology of early T-cell precursor acute lymphoblastic leukemia: the perfect trick.Biomarker research · 2021Review
- MutantCancer research · 2021Article
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Authors and funding
44 authors at 16 institutions in 8 countries.
Steven Goossens1] Vascular Cell Biology Unit, VIB Inflammation Research Center, Ghent University, Ghent B-9052, Belgium [2] Department for Biomedical Molecular Biology, Ghent University, Ghent B-9052, Belgium [3] Unit for Molecular and Cellular Oncology, VIB Inflammation Research Center, Ghent University, Ghent B-9052, Belgium [4] Mammalian Functional Genetics Laboratory, Division of Blood Cancers, Australian Centre for Blood Diseases, Department of Clinical Haematology, Monash University and Alfred Health Alfred Centre, 99 Commercial Road, Melbourne, Victoria 3004, Australia.
Enrico Radaelli1] Mouse and Animal Pathology Laboratory, Department of Veterinary Medicine, Università degli Studi di Milano, Milan 20122, Italy [2] VIB11 Center for the Biology of Disease, KU Leuven Center for Human Genetics, KU Leuven, Leuven B-3000, Belgium.
Odile Blanchet1] Institut Universitaire d'Hématologie and U944 INSERM, Hopital Saint-Louis, Paris 75010, France [2] Department of Hematology and Immunology, CHU, Angers 49100, France.
Kaat DurinckCenter for Medical Genetics, Ghent University Hospital, Ghent B-9000, Belgium.
Joni Van der MeulenCenter for Medical Genetics, Ghent University Hospital, Ghent B-9000, Belgium.
Sofie PeirsCenter for Medical Genetics, Ghent University Hospital, Ghent B-9000, Belgium.
Tom TaghonDepartment of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent B-9000, Belgium.
Cedric S TremblayStem Cell Research Group, Division of Blood Cancers, Australian Centre for Blood Diseases, Monash University, Melbourne, Victoria 3004, Australia.
Magdaline CostaMammalian Functional Genetics Laboratory, Division of Blood Cancers, Australian Centre for Blood Diseases, Department of Clinical Haematology, Monash University and Alfred Health Alfred Centre, 99 Commercial Road, Melbourne, Victoria 3004, Australia.
Morvarid Farhang Ghahremani1] Vascular Cell Biology Unit, VIB Inflammation Research Center, Ghent University, Ghent B-9052, Belgium [2] Department for Biomedical Molecular Biology, Ghent University, Ghent B-9052, Belgium.
Jelle De MedtsDepartment of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent B-9000, Belgium.
Sonia BartunkovaVascular Cell Biology Unit, VIB Inflammation Research Center, Ghent University, Ghent B-9052, Belgium.
Katharina Haigh1] Vascular Cell Biology Unit, VIB Inflammation Research Center, Ghent University, Ghent B-9052, Belgium [2] Department for Biomedical Molecular Biology, Ghent University, Ghent B-9052, Belgium [3] Mammalian Functional Genetics Laboratory, Division of Blood Cancers, Australian Centre for Blood Diseases, Department of Clinical Haematology, Monash University and Alfred Health Alfred Centre, 99 Commercial Road, Melbourne, Victoria 3004, Australia.
Claire SchwabNorthern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne NE2 4AD, UK.
Natalie Farla1] Vascular Cell Biology Unit, VIB Inflammation Research Center, Ghent University, Ghent B-9052, Belgium [2] Department for Biomedical Molecular Biology, Ghent University, Ghent B-9052, Belgium [3] Unit for Molecular and Cellular Oncology, VIB Inflammation Research Center, Ghent University, Ghent B-9052, Belgium.
Tim Pieters1] Vascular Cell Biology Unit, VIB Inflammation Research Center, Ghent University, Ghent B-9052, Belgium [2] Department for Biomedical Molecular Biology, Ghent University, Ghent B-9052, Belgium [3] Unit for Molecular and Cellular Oncology, VIB Inflammation Research Center, Ghent University, Ghent B-9052, Belgium [4] Center for Medical Genetics, Ghent University Hospital, Ghent B-9000, Belgium.
Filip MatthijssensCenter for Medical Genetics, Ghent University Hospital, Ghent B-9000, Belgium.
Nadine Van RoyCenter for Medical Genetics, Ghent University Hospital, Ghent B-9000, Belgium.
J Adam BestDivision of Biological Sciences, Section of Molecular Biology, University of California at San Diego, La Jolla, California 92093, USA.
Kim DeswarteVIB Inflammation Research Center, Ghent University, Ghent B-9052, Belgium.
Pieter BogaertDepartment for Biomedical Molecular Biology, Ghent University, Ghent B-9052, Belgium.
Catherine CarmichaelMammalian Functional Genetics Laboratory, Division of Blood Cancers, Australian Centre for Blood Diseases, Department of Clinical Haematology, Monash University and Alfred Health Alfred Centre, 99 Commercial Road, Melbourne, Victoria 3004, Australia.
Adam RickardMammalian Functional Genetics Laboratory, Division of Blood Cancers, Australian Centre for Blood Diseases, Department of Clinical Haematology, Monash University and Alfred Health Alfred Centre, 99 Commercial Road, Melbourne, Victoria 3004, Australia.
Santi SuryaniChildren's Cancer Institute, Leukaemia Biology Program, Lowy Cancer Research Centre, University of New South Wales, Sydney, New South Wales 2052, Australia.
Lauryn S BrackenChildren's Cancer Institute, Leukaemia Biology Program, Lowy Cancer Research Centre, University of New South Wales, Sydney, New South Wales 2052, Australia.
Raed AlserihiCancer and Haematology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne University, Parkville, Victoria 3052, Australia.
Kirsten Canté-BarrettDepartment of Pediatric Oncology/Hematology, Erasmus MC Rotterdam-Sophia Children's Hospital, Rotterdam 3015CE, The Netherlands.
Lieven Haenebalcke1] Vascular Cell Biology Unit, VIB Inflammation Research Center, Ghent University, Ghent B-9052, Belgium [2] Department for Biomedical Molecular Biology, Ghent University, Ghent B-9052, Belgium.
Emmanuelle Clappier1] Institut Universitaire d'Hématologie and U944 INSERM, Hopital Saint-Louis, Paris 75010, France [2] Department of Hematology and Immunology, CHU, Angers 49100, France.
Pieter RondouCenter for Medical Genetics, Ghent University Hospital, Ghent B-9000, Belgium.
Karolina Slowicka1] Vascular Cell Biology Unit, VIB Inflammation Research Center, Ghent University, Ghent B-9052, Belgium [2] Department for Biomedical Molecular Biology, Ghent University, Ghent B-9052, Belgium.
Danny Huylebroeck1] Department of Development and Regeneration, KU Leuven, Leuven B-3000, Belgium [2] Department of Cell Biology, Erasmus MC, Rotterdam 3015CE, The Netherlands.
Ananda W GoldrathDivision of Biological Sciences, Section of Molecular Biology, University of California at San Diego, La Jolla, California 92093, USA.
Viktor JanzenDepartment of Internal Medicine III, Hematology and Oncology, University of Bonn, D-53012 Bonn, Germany.
Matthew P McCormackCancer and Haematology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne University, Parkville, Victoria 3052, Australia.
Richard B LockChildren's Cancer Institute, Leukaemia Biology Program, Lowy Cancer Research Centre, University of New South Wales, Sydney, New South Wales 2052, Australia.
David J CurtisStem Cell Research Group, Division of Blood Cancers, Australian Centre for Blood Diseases, Monash University, Melbourne, Victoria 3004, Australia.
Christine HarrisonNorthern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne NE2 4AD, UK.
Geert Berx1] Department for Biomedical Molecular Biology, Ghent University, Ghent B-9052, Belgium [2] Unit for Molecular and Cellular Oncology, VIB Inflammation Research Center, Ghent University, Ghent B-9052, Belgium.
Frank SpelemanDepartment of Hematology and Immunology, CHU, Angers 49100, France.
Jules P P MeijerinkDepartment of Pediatric Oncology/Hematology, Erasmus MC Rotterdam-Sophia Children's Hospital, Rotterdam 3015CE, The Netherlands.
Jean Soulier1] Institut Universitaire d'Hématologie and U944 INSERM, Hopital Saint-Louis, Paris 75010, France [2] Department of Hematology and Immunology, CHU, Angers 49100, France.
Pieter Van VlierbergheCenter for Medical Genetics, Ghent University Hospital, Ghent B-9000, Belgium.
Jody J Haigh1] Vascular Cell Biology Unit, VIB Inflammation Research Center, Ghent University, Ghent B-9052, Belgium [2] Department for Biomedical Molecular Biology, Ghent University, Ghent B-9052, Belgium [3] Mammalian Functional Genetics Laboratory, Division of Blood Cancers, Australian Centre for Blood Diseases, Department of Clinical Haematology, Monash University and Alfred Health Alfred Centre, 99 Commercial Road, Melbourne, Victoria 3004, Australia.
Ghent University · BEGhent University Hospital · BEAlfred Health · AUMonash University · AUUNSW Sydney · AUCentre Hospitalier Universitaire d'Angers · FRErasmus MC - Sophia Children’s Hospital · NLHôpital Saint-Louis · FRNewcastle University · GBUniversity of California, San Diego · USVIB-UGent Center for Inflammation Research · BEKU Leuven · BEUniversity of Bonn · DEUniversity of Melbourne · AUUniversity of Milan · ITWalter and Eliza Hall Institute of Medical Research · AU
Funding
T cell maintenance: molecular mediators of the TCR-derived survival signalR01AI067545 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GOLDRATH, ANANDA W · 2006 to 2021
$6.1MT cell maintenance: molecular mediators of T cell differentiation and survivalR37AI067545 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Ananda W Goldrath · 2022 to 2026
$3.0MNIAID NIH HHS R37 AI067545
Abstract
Early T-cell precursor leukaemia (ETP-ALL) is a high-risk subtype of human leukaemia that is poorly understood at the molecular level. Here we report translocations targeting the zinc finger E-box-binding transcription factor ZEB2 as a recurrent genetic lesion in immature/ETP-ALL. Using a conditional gain-of-function mouse model, we demonstrate that sustained Zeb2 expression initiates T-cell leukaemia. Moreover, Zeb2-driven mouse leukaemia exhibit some features of the human immature/ETP-ALL gene expression signature, as well as an enhanced leukaemia-initiation potential and activated Janus kinase (JAK)/signal transducers and activators of transcription (STAT) signalling through transcriptional activation of IL7R. This study reveals ZEB2 as an oncogene in the biology of immature/ETP-ALL and paves the way towards pre-clinical studies of novel compounds for the treatment of this aggressive subtype of human T-ALL using our Zeb2-driven mouse model.
Indexed as
AnimalsBlotting, WesternChromatin ImmunoprecipitationFlow CytometryGene Expression ProfilingGene Expression Regulation, NeoplasticHistological TechniquesHomeodomain ProteinsHumansImmunohistochemistryIn Situ Hybridization, FluorescenceJanus KinasesKaplan-Meier EstimateKaryotypingLeukemia, T-CellLuciferasesHomeodomain ProteinsJanus KinasesLuciferasesReceptors, Interleukin-7Repressor ProteinsSTAT Transcription FactorsZEB2 protein, mouseZinc Finger E-box Binding Homeobox 2
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