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ZEB2 drives immature T-cell lymphoblastic leukaemia development via enhanced tumour-initiating potential and IL-7 receptor signalling.
Goossens, Steven; Radaelli, Enrico; Blanchet, Odile; Durinck, Kaat; Van der Meulen, Joni; Peirs, Sofie; Taghon, Tom; Tremblay, Cedric S; Costa, Magdaline; Farhang Ghahremani, Morvarid; De Medts, Jelle; Bartunkova, Sonia; Haigh, Katharina; Schwab, Claire; Farla, Natalie; Pieters, Tim; Matthijssens, Filip; Van Roy, Nadine; Best, J Adam; Deswarte, Kim; Bogaert, Pieter; Carmichael, Catherine; Rickard, Adam; Suryani, Santi; Bracken, Lauryn S; Alserihi, Raed; Canté-Barrett, Kirsten; Haenebalcke, Lieven; Clappier, Emmanuelle; Rondou, Pieter; Slowicka, Karolina; Huylebroeck, Danny; Goldrath, Ananda W; Janzen, Viktor; McCormack, Matthew P; Lock, Richard B; Curtis, David J; Harrison, Christine; Berx, Geert; Speleman, Frank; Meijerink, Jules P P; Soulier, Jean; Van Vlierberghe, Pieter; Haigh, Jody J.
  • Goossens S; 1] 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-
  • Radaelli E; 1] 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.
  • Blanchet O; 1] Institut Universitaire d'Hématologie and U944 INSERM, Hopital Saint-Louis, Paris 75010, France [2] Department of Hematology and Immunology, CHU, Angers 49100, France.
  • Durinck K; Center for Medical Genetics, Ghent University Hospital, Ghent B-9000, Belgium.
  • Van der Meulen J; Center for Medical Genetics, Ghent University Hospital, Ghent B-9000, Belgium.
  • Peirs S; Center for Medical Genetics, Ghent University Hospital, Ghent B-9000, Belgium.
  • Taghon T; Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent B-9000, Belgium.
  • Tremblay CS; Stem Cell Research Group, Division of Blood Cancers, Australian Centre for Blood Diseases, Monash University, Melbourne, Victoria 3004, Australia.
  • Costa M; 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.
  • Farhang Ghahremani M; 1] 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.
  • De Medts J; Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent B-9000, Belgium.
  • Bartunkova S; Vascular Cell Biology Unit, VIB Inflammation Research Center, Ghent University, Ghent B-9052, Belgium.
  • Haigh K; 1] 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 Disea
  • Schwab C; Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne NE2 4AD, UK.
  • Farla N; 1] 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-
  • Pieters T; 1] 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-
  • Matthijssens F; Center for Medical Genetics, Ghent University Hospital, Ghent B-9000, Belgium.
  • Van Roy N; Center for Medical Genetics, Ghent University Hospital, Ghent B-9000, Belgium.
  • Best JA; Division of Biological Sciences, Section of Molecular Biology, University of California at San Diego, La Jolla, California 92093, USA.
  • Deswarte K; VIB Inflammation Research Center, Ghent University, Ghent B-9052, Belgium.
  • Bogaert P; Department for Biomedical Molecular Biology, Ghent University, Ghent B-9052, Belgium.
  • Carmichael C; 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.
  • Rickard A; 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.
  • Suryani S; Children's Cancer Institute, Leukaemia Biology Program, Lowy Cancer Research Centre, University of New South Wales, Sydney, New South Wales 2052, Australia.
  • Bracken LS; Children's Cancer Institute, Leukaemia Biology Program, Lowy Cancer Research Centre, University of New South Wales, Sydney, New South Wales 2052, Australia.
  • Alserihi R; Cancer and Haematology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne University, Parkville, Victoria 3052, Australia.
  • Canté-Barrett K; Department of Pediatric Oncology/Hematology, Erasmus MC Rotterdam-Sophia Children's Hospital, Rotterdam 3015CE, The Netherlands.
  • Haenebalcke L; 1] 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.
  • Clappier E; 1] Institut Universitaire d'Hématologie and U944 INSERM, Hopital Saint-Louis, Paris 75010, France [2] Department of Hematology and Immunology, CHU, Angers 49100, France.
  • Rondou P; Center for Medical Genetics, Ghent University Hospital, Ghent B-9000, Belgium.
  • Slowicka K; 1] 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.
  • Huylebroeck D; 1] Department of Development and Regeneration, KU Leuven, Leuven B-3000, Belgium [2] Department of Cell Biology, Erasmus MC, Rotterdam 3015CE, The Netherlands.
  • Goldrath AW; Division of Biological Sciences, Section of Molecular Biology, University of California at San Diego, La Jolla, California 92093, USA.
  • Janzen V; Department of Internal Medicine III, Hematology and Oncology, University of Bonn, D-53012 Bonn, Germany.
  • McCormack MP; Cancer and Haematology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne University, Parkville, Victoria 3052, Australia.
  • Lock RB; Children's Cancer Institute, Leukaemia Biology Program, Lowy Cancer Research Centre, University of New South Wales, Sydney, New South Wales 2052, Australia.
  • Curtis DJ; Stem Cell Research Group, Division of Blood Cancers, Australian Centre for Blood Diseases, Monash University, Melbourne, Victoria 3004, Australia.
  • Harrison C; Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne NE2 4AD, UK.
  • Berx G; 1] 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.
  • Speleman F; Department of Hematology and Immunology, CHU, Angers 49100, France.
  • Meijerink JP; Department of Pediatric Oncology/Hematology, Erasmus MC Rotterdam-Sophia Children's Hospital, Rotterdam 3015CE, The Netherlands.
  • Soulier J; 1] Institut Universitaire d'Hématologie and U944 INSERM, Hopital Saint-Louis, Paris 75010, France [2] Department of Hematology and Immunology, CHU, Angers 49100, France.
  • Van Vlierberghe P; Center for Medical Genetics, Ghent University Hospital, Ghent B-9000, Belgium.
  • Haigh JJ; 1] 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 Disea
Nat Commun ; 6: 5794, 2015 Jan 07.
Article en En | MEDLINE | ID: mdl-25565005
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.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Proteínas Represoras / Leucemia de Células T / Transducción de Señal / Regulación Neoplásica de la Expresión Génica / Proteínas de Homeodominio Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Año: 2015 Tipo del documento: Article
Texto completo
Imprimir
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Proteínas Represoras / Leucemia de Células T / Transducción de Señal / Regulación Neoplásica de la Expresión Génica / Proteínas de Homeodominio Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Año: 2015 Tipo del documento: Article