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ZEB2 drives immature T-cell lymphoblastic leukaemia development via enhanced tumour-initiating potential and IL-7 receptor signalling.

Identifieur interne : 003021 ( PubMed/Curation ); précédent : 003020; suivant : 003022

ZEB2 drives immature T-cell lymphoblastic leukaemia development via enhanced tumour-initiating potential and IL-7 receptor signalling.

Auteurs : Steven Goossens [Australie] ; Enrico Radaelli [Belgique] ; Odile Blanchet [France] ; Kaat Durinck [Belgique] ; Joni Van Der Meulen [Belgique] ; Sofie Peirs [Belgique] ; Tom Taghon [Belgique] ; Cedric S. Tremblay [Australie] ; Magdaline Costa [Australie] ; Morvarid Farhang Ghahremani [Belgique] ; Jelle De Medts [Belgique] ; Sonia Bartunkova [Belgique] ; Katharina Haigh [Australie] ; Claire Schwab [Royaume-Uni] ; Natalie Farla [Belgique] ; Tim Pieters [Belgique] ; Filip Matthijssens [Belgique] ; Nadine Van Roy [Belgique] ; J Adam Best [États-Unis] ; Kim Deswarte [Belgique] ; Pieter Bogaert [Belgique] ; Catherine Carmichael [Australie] ; Adam Rickard [Australie] ; Santi Suryani [Australie] ; Lauryn S. Bracken [Australie] ; Raed Alserihi [Australie] ; Kirsten Canté-Barrett [Pays-Bas] ; Lieven Haenebalcke [Belgique] ; Emmanuelle Clappier [France] ; Pieter Rondou [Belgique] ; Karolina Slowicka [Belgique] ; Danny Huylebroeck [Pays-Bas] ; Ananda W. Goldrath [États-Unis] ; Viktor Janzen [Allemagne] ; Matthew P. Mccormack [Australie] ; Richard B. Lock [Australie] ; David J. Curtis [Australie] ; Christine Harrison [Royaume-Uni] ; Geert Berx [Belgique] ; Frank Speleman [France] ; Jules P P. Meijerink [Pays-Bas] ; Jean Soulier [France] ; Pieter Van Vlierberghe [Belgique] ; Jody J. Haigh [Australie]

Source :

Nature communications [ 2041-1723 ] ; 2015.

RBID : pubmed:25565005

Descripteurs français

English descriptors

KwdEn :
- Animals, Blotting, Western, Chromatin Immunoprecipitation, Flow Cytometry, Gene Expression Profiling, Gene Expression Regulation, Neoplastic (genetics), Gene Expression Regulation, Neoplastic (physiology), Histological Techniques, Homeodomain Proteins (genetics), Homeodomain Proteins (immunology), Humans, Immunohistochemistry, In Situ Hybridization, Fluorescence, Janus Kinases (metabolism), Kaplan-Meier Estimate, Karyotyping, Leukemia, T-Cell (physiopathology), Luciferases, Mice, Real-Time Polymerase Chain Reaction, Receptors, Interleukin-7 (metabolism), Repressor Proteins (genetics), Repressor Proteins (immunology), STAT Transcription Factors (metabolism), Signal Transduction (genetics), Signal Transduction (physiology).
MESH :
- chemical , genetics : Homeodomain Proteins, Repressor Proteins.
- genetics : Gene Expression Regulation, Neoplastic, Signal Transduction.
- chemical , immunology : Homeodomain Proteins, Repressor Proteins.
- chemical , metabolism : Janus Kinases, Receptors, Interleukin-7, STAT Transcription Factors.
- physiology : Gene Expression Regulation, Neoplastic, Signal Transduction.
- physiopathology : Leukemia, T-Cell.
- Animals, Blotting, Western, Chromatin Immunoprecipitation, Flow Cytometry, Gene Expression Profiling, Histological Techniques, Humans, Immunohistochemistry, In Situ Hybridization, Fluorescence, Kaplan-Meier Estimate, Karyotyping, Luciferases, Mice, Real-Time Polymerase Chain Reaction.

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.

DOI: 10.1038/ncomms6794
PubMed: 25565005

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<author><name sortKey="Taghon, Tom" sort="Taghon, Tom" uniqKey="Taghon T" first="Tom" last="Taghon">Tom Taghon</name>
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<author><name sortKey="Tremblay, Cedric S" sort="Tremblay, Cedric S" uniqKey="Tremblay C" first="Cedric S" last="Tremblay">Cedric S. Tremblay</name>
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<author><name sortKey="Farhang Ghahremani, Morvarid" sort="Farhang Ghahremani, Morvarid" uniqKey="Farhang Ghahremani M" first="Morvarid" last="Farhang Ghahremani">Morvarid Farhang Ghahremani</name>
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<country xml:lang="fr">Belgique</country>
<wicri:regionArea>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</wicri:regionArea>
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<author><name sortKey="De Medts, Jelle" sort="De Medts, Jelle" uniqKey="De Medts J" first="Jelle" last="De Medts">Jelle De Medts</name>
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<country xml:lang="fr">Belgique</country>
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<author><name sortKey="Schwab, Claire" sort="Schwab, Claire" uniqKey="Schwab C" first="Claire" last="Schwab">Claire Schwab</name>
<affiliation wicri:level="1"><nlm:affiliation>Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne NE2 4AD, UK.</nlm:affiliation>
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<author><name sortKey="Farla, Natalie" sort="Farla, Natalie" uniqKey="Farla N" first="Natalie" last="Farla">Natalie Farla</name>
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<country xml:lang="fr">Belgique</country>
<wicri:regionArea>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-9052</wicri:regionArea>
</affiliation>
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<author><name sortKey="Pieters, Tim" sort="Pieters, Tim" uniqKey="Pieters T" first="Tim" last="Pieters">Tim Pieters</name>
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<country xml:lang="fr">Belgique</country>
<wicri:regionArea>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-9052, Belgium [4] Center for Medical Genetics, Ghent University Hospital, Ghent B-9000</wicri:regionArea>
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<author><name sortKey="Matthijssens, Filip" sort="Matthijssens, Filip" uniqKey="Matthijssens F" first="Filip" last="Matthijssens">Filip Matthijssens</name>
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<author><name sortKey="Van Roy, Nadine" sort="Van Roy, Nadine" uniqKey="Van Roy N" first="Nadine" last="Van Roy">Nadine Van Roy</name>
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<author><name sortKey="Best, J Adam" sort="Best, J Adam" uniqKey="Best J" first="J Adam" last="Best">J Adam Best</name>
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<author><name sortKey="Deswarte, Kim" sort="Deswarte, Kim" uniqKey="Deswarte K" first="Kim" last="Deswarte">Kim Deswarte</name>
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<country xml:lang="fr">Belgique</country>
<wicri:regionArea>VIB Inflammation Research Center, Ghent University, Ghent B-9052</wicri:regionArea>
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<author><name sortKey="Bogaert, Pieter" sort="Bogaert, Pieter" uniqKey="Bogaert P" first="Pieter" last="Bogaert">Pieter Bogaert</name>
<affiliation wicri:level="1"><nlm:affiliation>Department for Biomedical Molecular Biology, Ghent University, Ghent B-9052, Belgium.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Department for Biomedical Molecular Biology, Ghent University, Ghent B-9052</wicri:regionArea>
</affiliation>
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<author><name sortKey="Carmichael, Catherine" sort="Carmichael, Catherine" uniqKey="Carmichael C" first="Catherine" last="Carmichael">Catherine Carmichael</name>
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<country xml:lang="fr">Australie</country>
<wicri:regionArea>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</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Rickard, Adam" sort="Rickard, Adam" uniqKey="Rickard A" first="Adam" last="Rickard">Adam Rickard</name>
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<country xml:lang="fr">Australie</country>
<wicri:regionArea>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</wicri:regionArea>
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</author>
<author><name sortKey="Suryani, Santi" sort="Suryani, Santi" uniqKey="Suryani S" first="Santi" last="Suryani">Santi Suryani</name>
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<country xml:lang="fr">Australie</country>
<wicri:regionArea>Children's Cancer Institute, Leukaemia Biology Program, Lowy Cancer Research Centre, University of New South Wales, Sydney, New South Wales 2052</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bracken, Lauryn S" sort="Bracken, Lauryn S" uniqKey="Bracken L" first="Lauryn S" last="Bracken">Lauryn S. Bracken</name>
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<country xml:lang="fr">Australie</country>
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</author>
<author><name sortKey="Alserihi, Raed" sort="Alserihi, Raed" uniqKey="Alserihi R" first="Raed" last="Alserihi">Raed Alserihi</name>
<affiliation wicri:level="1"><nlm:affiliation>Cancer and Haematology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne University, Parkville, Victoria 3052, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Cancer and Haematology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne University, Parkville, Victoria 3052</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Cante Barrett, Kirsten" sort="Cante Barrett, Kirsten" uniqKey="Cante Barrett K" first="Kirsten" last="Canté-Barrett">Kirsten Canté-Barrett</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Pediatric Oncology/Hematology, Erasmus MC Rotterdam-Sophia Children's Hospital, Rotterdam 3015CE, The Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Pediatric Oncology/Hematology, Erasmus MC Rotterdam-Sophia Children's Hospital, Rotterdam 3015CE</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Haenebalcke, Lieven" sort="Haenebalcke, Lieven" uniqKey="Haenebalcke L" first="Lieven" last="Haenebalcke">Lieven Haenebalcke</name>
<affiliation wicri:level="1"><nlm:affiliation>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.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>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</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Clappier, Emmanuelle" sort="Clappier, Emmanuelle" uniqKey="Clappier E" first="Emmanuelle" last="Clappier">Emmanuelle Clappier</name>
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<country xml:lang="fr">France</country>
<wicri:regionArea>1] Institut Universitaire d'Hématologie and U944 INSERM, Hopital Saint-Louis, Paris 75010, France [2] Department of Hematology and Immunology, CHU, Angers 49100</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Rondou, Pieter" sort="Rondou, Pieter" uniqKey="Rondou P" first="Pieter" last="Rondou">Pieter Rondou</name>
<affiliation wicri:level="1"><nlm:affiliation>Center for Medical Genetics, Ghent University Hospital, Ghent B-9000, Belgium.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Center for Medical Genetics, Ghent University Hospital, Ghent B-9000</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Slowicka, Karolina" sort="Slowicka, Karolina" uniqKey="Slowicka K" first="Karolina" last="Slowicka">Karolina Slowicka</name>
<affiliation wicri:level="1"><nlm:affiliation>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.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>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</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Huylebroeck, Danny" sort="Huylebroeck, Danny" uniqKey="Huylebroeck D" first="Danny" last="Huylebroeck">Danny Huylebroeck</name>
<affiliation wicri:level="1"><nlm:affiliation>1] Department of Development and Regeneration, KU Leuven, Leuven B-3000, Belgium [2] Department of Cell Biology, Erasmus MC, Rotterdam 3015CE, The Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>1] Department of Development and Regeneration, KU Leuven, Leuven B-3000, Belgium [2] Department of Cell Biology, Erasmus MC, Rotterdam 3015CE</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Goldrath, Ananda W" sort="Goldrath, Ananda W" uniqKey="Goldrath A" first="Ananda W" last="Goldrath">Ananda W. Goldrath</name>
<affiliation wicri:level="1"><nlm:affiliation>Division of Biological Sciences, Section of Molecular Biology, University of California at San Diego, La Jolla, California 92093, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Biological Sciences, Section of Molecular Biology, University of California at San Diego, La Jolla, California 92093</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Janzen, Viktor" sort="Janzen, Viktor" uniqKey="Janzen V" first="Viktor" last="Janzen">Viktor Janzen</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Internal Medicine III, Hematology and Oncology, University of Bonn, D-53012 Bonn, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Internal Medicine III, Hematology and Oncology, University of Bonn, D-53012 Bonn</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Mccormack, Matthew P" sort="Mccormack, Matthew P" uniqKey="Mccormack M" first="Matthew P" last="Mccormack">Matthew P. Mccormack</name>
<affiliation wicri:level="1"><nlm:affiliation>Cancer and Haematology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne University, Parkville, Victoria 3052, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Cancer and Haematology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne University, Parkville, Victoria 3052</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Lock, Richard B" sort="Lock, Richard B" uniqKey="Lock R" first="Richard B" last="Lock">Richard B. Lock</name>
<affiliation wicri:level="1"><nlm:affiliation>Children's Cancer Institute, Leukaemia Biology Program, Lowy Cancer Research Centre, University of New South Wales, Sydney, New South Wales 2052, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Children's Cancer Institute, Leukaemia Biology Program, Lowy Cancer Research Centre, University of New South Wales, Sydney, New South Wales 2052</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Curtis, David J" sort="Curtis, David J" uniqKey="Curtis D" first="David J" last="Curtis">David J. Curtis</name>
<affiliation wicri:level="1"><nlm:affiliation>Stem Cell Research Group, Division of Blood Cancers, Australian Centre for Blood Diseases, Monash University, Melbourne, Victoria 3004, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Stem Cell Research Group, Division of Blood Cancers, Australian Centre for Blood Diseases, Monash University, Melbourne, Victoria 3004</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Harrison, Christine" sort="Harrison, Christine" uniqKey="Harrison C" first="Christine" last="Harrison">Christine Harrison</name>
<affiliation wicri:level="1"><nlm:affiliation>Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne NE2 4AD, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne NE2 4AD</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Berx, Geert" sort="Berx, Geert" uniqKey="Berx G" first="Geert" last="Berx">Geert Berx</name>
<affiliation wicri:level="1"><nlm:affiliation>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.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>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</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Speleman, Frank" sort="Speleman, Frank" uniqKey="Speleman F" first="Frank" last="Speleman">Frank Speleman</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Hematology and Immunology, CHU, Angers 49100, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Department of Hematology and Immunology, CHU, Angers 49100</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Meijerink, Jules P P" sort="Meijerink, Jules P P" uniqKey="Meijerink J" first="Jules P P" last="Meijerink">Jules P P. Meijerink</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Pediatric Oncology/Hematology, Erasmus MC Rotterdam-Sophia Children's Hospital, Rotterdam 3015CE, The Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Pediatric Oncology/Hematology, Erasmus MC Rotterdam-Sophia Children's Hospital, Rotterdam 3015CE</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Soulier, Jean" sort="Soulier, Jean" uniqKey="Soulier J" first="Jean" last="Soulier">Jean Soulier</name>
<affiliation wicri:level="1"><nlm:affiliation>1] Institut Universitaire d'Hématologie and U944 INSERM, Hopital Saint-Louis, Paris 75010, France [2] Department of Hematology and Immunology, CHU, Angers 49100, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>1] Institut Universitaire d'Hématologie and U944 INSERM, Hopital Saint-Louis, Paris 75010, France [2] Department of Hematology and Immunology, CHU, Angers 49100</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Van Vlierberghe, Pieter" sort="Van Vlierberghe, Pieter" uniqKey="Van Vlierberghe P" first="Pieter" last="Van Vlierberghe">Pieter Van Vlierberghe</name>
<affiliation wicri:level="1"><nlm:affiliation>Center for Medical Genetics, Ghent University Hospital, Ghent B-9000, Belgium.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Center for Medical Genetics, Ghent University Hospital, Ghent B-9000</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Haigh, Jody J" sort="Haigh, Jody J" uniqKey="Haigh J" first="Jody J" last="Haigh">Jody J. Haigh</name>
<affiliation wicri:level="1"><nlm:affiliation>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 Diseases, Department of Clinical Haematology, Monash University and Alfred Health Alfred Centre, 99 Commercial Road, Melbourne, Victoria 3004, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>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 Diseases, Department of Clinical Haematology, Monash University and Alfred Health Alfred Centre, 99 Commercial Road, Melbourne, Victoria 3004</wicri:regionArea>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PubMed</idno>
<date when="2015">2015</date>
<idno type="RBID">pubmed:25565005</idno>
<idno type="pmid">25565005</idno>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">ZEB2 drives immature T-cell lymphoblastic leukaemia development via enhanced tumour-initiating potential and IL-7 receptor signalling.</title>
<author><name sortKey="Goossens, Steven" sort="Goossens, Steven" uniqKey="Goossens S" first="Steven" last="Goossens">Steven Goossens</name>
<affiliation wicri:level="1"><nlm:affiliation>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-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.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>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-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</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Radaelli, Enrico" sort="Radaelli, Enrico" uniqKey="Radaelli E" first="Enrico" last="Radaelli">Enrico Radaelli</name>
<affiliation wicri:level="1"><nlm:affiliation>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.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>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</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Blanchet, Odile" sort="Blanchet, Odile" uniqKey="Blanchet O" first="Odile" last="Blanchet">Odile Blanchet</name>
<affiliation wicri:level="1"><nlm:affiliation>1] Institut Universitaire d'Hématologie and U944 INSERM, Hopital Saint-Louis, Paris 75010, France [2] Department of Hematology and Immunology, CHU, Angers 49100, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>1] Institut Universitaire d'Hématologie and U944 INSERM, Hopital Saint-Louis, Paris 75010, France [2] Department of Hematology and Immunology, CHU, Angers 49100</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Durinck, Kaat" sort="Durinck, Kaat" uniqKey="Durinck K" first="Kaat" last="Durinck">Kaat Durinck</name>
<affiliation wicri:level="1"><nlm:affiliation>Center for Medical Genetics, Ghent University Hospital, Ghent B-9000, Belgium.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Center for Medical Genetics, Ghent University Hospital, Ghent B-9000</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Van Der Meulen, Joni" sort="Van Der Meulen, Joni" uniqKey="Van Der Meulen J" first="Joni" last="Van Der Meulen">Joni Van Der Meulen</name>
<affiliation wicri:level="1"><nlm:affiliation>Center for Medical Genetics, Ghent University Hospital, Ghent B-9000, Belgium.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Center for Medical Genetics, Ghent University Hospital, Ghent B-9000</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Peirs, Sofie" sort="Peirs, Sofie" uniqKey="Peirs S" first="Sofie" last="Peirs">Sofie Peirs</name>
<affiliation wicri:level="1"><nlm:affiliation>Center for Medical Genetics, Ghent University Hospital, Ghent B-9000, Belgium.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Center for Medical Genetics, Ghent University Hospital, Ghent B-9000</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Taghon, Tom" sort="Taghon, Tom" uniqKey="Taghon T" first="Tom" last="Taghon">Tom Taghon</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent B-9000, Belgium.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent B-9000</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Tremblay, Cedric S" sort="Tremblay, Cedric S" uniqKey="Tremblay C" first="Cedric S" last="Tremblay">Cedric S. Tremblay</name>
<affiliation wicri:level="1"><nlm:affiliation>Stem Cell Research Group, Division of Blood Cancers, Australian Centre for Blood Diseases, Monash University, Melbourne, Victoria 3004, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Stem Cell Research Group, Division of Blood Cancers, Australian Centre for Blood Diseases, Monash University, Melbourne, Victoria 3004</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Costa, Magdaline" sort="Costa, Magdaline" uniqKey="Costa M" first="Magdaline" last="Costa">Magdaline Costa</name>
<affiliation wicri:level="1"><nlm:affiliation>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.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>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</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Farhang Ghahremani, Morvarid" sort="Farhang Ghahremani, Morvarid" uniqKey="Farhang Ghahremani M" first="Morvarid" last="Farhang Ghahremani">Morvarid Farhang Ghahremani</name>
<affiliation wicri:level="1"><nlm:affiliation>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.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>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</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="De Medts, Jelle" sort="De Medts, Jelle" uniqKey="De Medts J" first="Jelle" last="De Medts">Jelle De Medts</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent B-9000, Belgium.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent B-9000</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bartunkova, Sonia" sort="Bartunkova, Sonia" uniqKey="Bartunkova S" first="Sonia" last="Bartunkova">Sonia Bartunkova</name>
<affiliation wicri:level="1"><nlm:affiliation>Vascular Cell Biology Unit, VIB Inflammation Research Center, Ghent University, Ghent B-9052, Belgium.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Vascular Cell Biology Unit, VIB Inflammation Research Center, Ghent University, Ghent B-9052</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Haigh, Katharina" sort="Haigh, Katharina" uniqKey="Haigh K" first="Katharina" last="Haigh">Katharina Haigh</name>
<affiliation wicri:level="1"><nlm:affiliation>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 Diseases, Department of Clinical Haematology, Monash University and Alfred Health Alfred Centre, 99 Commercial Road, Melbourne, Victoria 3004, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>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 Diseases, Department of Clinical Haematology, Monash University and Alfred Health Alfred Centre, 99 Commercial Road, Melbourne, Victoria 3004</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Schwab, Claire" sort="Schwab, Claire" uniqKey="Schwab C" first="Claire" last="Schwab">Claire Schwab</name>
<affiliation wicri:level="1"><nlm:affiliation>Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne NE2 4AD, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne NE2 4AD</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Farla, Natalie" sort="Farla, Natalie" uniqKey="Farla N" first="Natalie" last="Farla">Natalie Farla</name>
<affiliation wicri:level="1"><nlm:affiliation>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-9052, Belgium.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>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-9052</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Pieters, Tim" sort="Pieters, Tim" uniqKey="Pieters T" first="Tim" last="Pieters">Tim Pieters</name>
<affiliation wicri:level="1"><nlm:affiliation>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-9052, Belgium [4] Center for Medical Genetics, Ghent University Hospital, Ghent B-9000, Belgium.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>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-9052, Belgium [4] Center for Medical Genetics, Ghent University Hospital, Ghent B-9000</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Matthijssens, Filip" sort="Matthijssens, Filip" uniqKey="Matthijssens F" first="Filip" last="Matthijssens">Filip Matthijssens</name>
<affiliation wicri:level="1"><nlm:affiliation>Center for Medical Genetics, Ghent University Hospital, Ghent B-9000, Belgium.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Center for Medical Genetics, Ghent University Hospital, Ghent B-9000</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Van Roy, Nadine" sort="Van Roy, Nadine" uniqKey="Van Roy N" first="Nadine" last="Van Roy">Nadine Van Roy</name>
<affiliation wicri:level="1"><nlm:affiliation>Center for Medical Genetics, Ghent University Hospital, Ghent B-9000, Belgium.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Center for Medical Genetics, Ghent University Hospital, Ghent B-9000</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Best, J Adam" sort="Best, J Adam" uniqKey="Best J" first="J Adam" last="Best">J Adam Best</name>
<affiliation wicri:level="1"><nlm:affiliation>Division of Biological Sciences, Section of Molecular Biology, University of California at San Diego, La Jolla, California 92093, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Biological Sciences, Section of Molecular Biology, University of California at San Diego, La Jolla, California 92093</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Deswarte, Kim" sort="Deswarte, Kim" uniqKey="Deswarte K" first="Kim" last="Deswarte">Kim Deswarte</name>
<affiliation wicri:level="1"><nlm:affiliation>VIB Inflammation Research Center, Ghent University, Ghent B-9052, Belgium.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>VIB Inflammation Research Center, Ghent University, Ghent B-9052</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bogaert, Pieter" sort="Bogaert, Pieter" uniqKey="Bogaert P" first="Pieter" last="Bogaert">Pieter Bogaert</name>
<affiliation wicri:level="1"><nlm:affiliation>Department for Biomedical Molecular Biology, Ghent University, Ghent B-9052, Belgium.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Department for Biomedical Molecular Biology, Ghent University, Ghent B-9052</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Carmichael, Catherine" sort="Carmichael, Catherine" uniqKey="Carmichael C" first="Catherine" last="Carmichael">Catherine Carmichael</name>
<affiliation wicri:level="1"><nlm:affiliation>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.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>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</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Rickard, Adam" sort="Rickard, Adam" uniqKey="Rickard A" first="Adam" last="Rickard">Adam Rickard</name>
<affiliation wicri:level="1"><nlm:affiliation>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.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>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</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Suryani, Santi" sort="Suryani, Santi" uniqKey="Suryani S" first="Santi" last="Suryani">Santi Suryani</name>
<affiliation wicri:level="1"><nlm:affiliation>Children's Cancer Institute, Leukaemia Biology Program, Lowy Cancer Research Centre, University of New South Wales, Sydney, New South Wales 2052, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Children's Cancer Institute, Leukaemia Biology Program, Lowy Cancer Research Centre, University of New South Wales, Sydney, New South Wales 2052</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bracken, Lauryn S" sort="Bracken, Lauryn S" uniqKey="Bracken L" first="Lauryn S" last="Bracken">Lauryn S. Bracken</name>
<affiliation wicri:level="1"><nlm:affiliation>Children's Cancer Institute, Leukaemia Biology Program, Lowy Cancer Research Centre, University of New South Wales, Sydney, New South Wales 2052, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Children's Cancer Institute, Leukaemia Biology Program, Lowy Cancer Research Centre, University of New South Wales, Sydney, New South Wales 2052</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Alserihi, Raed" sort="Alserihi, Raed" uniqKey="Alserihi R" first="Raed" last="Alserihi">Raed Alserihi</name>
<affiliation wicri:level="1"><nlm:affiliation>Cancer and Haematology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne University, Parkville, Victoria 3052, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Cancer and Haematology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne University, Parkville, Victoria 3052</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Cante Barrett, Kirsten" sort="Cante Barrett, Kirsten" uniqKey="Cante Barrett K" first="Kirsten" last="Canté-Barrett">Kirsten Canté-Barrett</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Pediatric Oncology/Hematology, Erasmus MC Rotterdam-Sophia Children's Hospital, Rotterdam 3015CE, The Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Pediatric Oncology/Hematology, Erasmus MC Rotterdam-Sophia Children's Hospital, Rotterdam 3015CE</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Haenebalcke, Lieven" sort="Haenebalcke, Lieven" uniqKey="Haenebalcke L" first="Lieven" last="Haenebalcke">Lieven Haenebalcke</name>
<affiliation wicri:level="1"><nlm:affiliation>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.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>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</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Clappier, Emmanuelle" sort="Clappier, Emmanuelle" uniqKey="Clappier E" first="Emmanuelle" last="Clappier">Emmanuelle Clappier</name>
<affiliation wicri:level="1"><nlm:affiliation>1] Institut Universitaire d'Hématologie and U944 INSERM, Hopital Saint-Louis, Paris 75010, France [2] Department of Hematology and Immunology, CHU, Angers 49100, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>1] Institut Universitaire d'Hématologie and U944 INSERM, Hopital Saint-Louis, Paris 75010, France [2] Department of Hematology and Immunology, CHU, Angers 49100</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Rondou, Pieter" sort="Rondou, Pieter" uniqKey="Rondou P" first="Pieter" last="Rondou">Pieter Rondou</name>
<affiliation wicri:level="1"><nlm:affiliation>Center for Medical Genetics, Ghent University Hospital, Ghent B-9000, Belgium.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Center for Medical Genetics, Ghent University Hospital, Ghent B-9000</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Slowicka, Karolina" sort="Slowicka, Karolina" uniqKey="Slowicka K" first="Karolina" last="Slowicka">Karolina Slowicka</name>
<affiliation wicri:level="1"><nlm:affiliation>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.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>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</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Huylebroeck, Danny" sort="Huylebroeck, Danny" uniqKey="Huylebroeck D" first="Danny" last="Huylebroeck">Danny Huylebroeck</name>
<affiliation wicri:level="1"><nlm:affiliation>1] Department of Development and Regeneration, KU Leuven, Leuven B-3000, Belgium [2] Department of Cell Biology, Erasmus MC, Rotterdam 3015CE, The Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>1] Department of Development and Regeneration, KU Leuven, Leuven B-3000, Belgium [2] Department of Cell Biology, Erasmus MC, Rotterdam 3015CE</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Goldrath, Ananda W" sort="Goldrath, Ananda W" uniqKey="Goldrath A" first="Ananda W" last="Goldrath">Ananda W. Goldrath</name>
<affiliation wicri:level="1"><nlm:affiliation>Division of Biological Sciences, Section of Molecular Biology, University of California at San Diego, La Jolla, California 92093, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Biological Sciences, Section of Molecular Biology, University of California at San Diego, La Jolla, California 92093</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Janzen, Viktor" sort="Janzen, Viktor" uniqKey="Janzen V" first="Viktor" last="Janzen">Viktor Janzen</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Internal Medicine III, Hematology and Oncology, University of Bonn, D-53012 Bonn, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Internal Medicine III, Hematology and Oncology, University of Bonn, D-53012 Bonn</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Mccormack, Matthew P" sort="Mccormack, Matthew P" uniqKey="Mccormack M" first="Matthew P" last="Mccormack">Matthew P. Mccormack</name>
<affiliation wicri:level="1"><nlm:affiliation>Cancer and Haematology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne University, Parkville, Victoria 3052, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Cancer and Haematology Division, Walter and Eliza Hall Institute of Medical Research, Melbourne University, Parkville, Victoria 3052</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Lock, Richard B" sort="Lock, Richard B" uniqKey="Lock R" first="Richard B" last="Lock">Richard B. Lock</name>
<affiliation wicri:level="1"><nlm:affiliation>Children's Cancer Institute, Leukaemia Biology Program, Lowy Cancer Research Centre, University of New South Wales, Sydney, New South Wales 2052, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Children's Cancer Institute, Leukaemia Biology Program, Lowy Cancer Research Centre, University of New South Wales, Sydney, New South Wales 2052</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Curtis, David J" sort="Curtis, David J" uniqKey="Curtis D" first="David J" last="Curtis">David J. Curtis</name>
<affiliation wicri:level="1"><nlm:affiliation>Stem Cell Research Group, Division of Blood Cancers, Australian Centre for Blood Diseases, Monash University, Melbourne, Victoria 3004, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Stem Cell Research Group, Division of Blood Cancers, Australian Centre for Blood Diseases, Monash University, Melbourne, Victoria 3004</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Harrison, Christine" sort="Harrison, Christine" uniqKey="Harrison C" first="Christine" last="Harrison">Christine Harrison</name>
<affiliation wicri:level="1"><nlm:affiliation>Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne NE2 4AD, UK.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne NE2 4AD</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Berx, Geert" sort="Berx, Geert" uniqKey="Berx G" first="Geert" last="Berx">Geert Berx</name>
<affiliation wicri:level="1"><nlm:affiliation>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.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>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</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Speleman, Frank" sort="Speleman, Frank" uniqKey="Speleman F" first="Frank" last="Speleman">Frank Speleman</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Hematology and Immunology, CHU, Angers 49100, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Department of Hematology and Immunology, CHU, Angers 49100</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Meijerink, Jules P P" sort="Meijerink, Jules P P" uniqKey="Meijerink J" first="Jules P P" last="Meijerink">Jules P P. Meijerink</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Pediatric Oncology/Hematology, Erasmus MC Rotterdam-Sophia Children's Hospital, Rotterdam 3015CE, The Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Pediatric Oncology/Hematology, Erasmus MC Rotterdam-Sophia Children's Hospital, Rotterdam 3015CE</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Soulier, Jean" sort="Soulier, Jean" uniqKey="Soulier J" first="Jean" last="Soulier">Jean Soulier</name>
<affiliation wicri:level="1"><nlm:affiliation>1] Institut Universitaire d'Hématologie and U944 INSERM, Hopital Saint-Louis, Paris 75010, France [2] Department of Hematology and Immunology, CHU, Angers 49100, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>1] Institut Universitaire d'Hématologie and U944 INSERM, Hopital Saint-Louis, Paris 75010, France [2] Department of Hematology and Immunology, CHU, Angers 49100</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Van Vlierberghe, Pieter" sort="Van Vlierberghe, Pieter" uniqKey="Van Vlierberghe P" first="Pieter" last="Van Vlierberghe">Pieter Van Vlierberghe</name>
<affiliation wicri:level="1"><nlm:affiliation>Center for Medical Genetics, Ghent University Hospital, Ghent B-9000, Belgium.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Center for Medical Genetics, Ghent University Hospital, Ghent B-9000</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Haigh, Jody J" sort="Haigh, Jody J" uniqKey="Haigh J" first="Jody J" last="Haigh">Jody J. Haigh</name>
<affiliation wicri:level="1"><nlm:affiliation>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 Diseases, Department of Clinical Haematology, Monash University and Alfred Health Alfred Centre, 99 Commercial Road, Melbourne, Victoria 3004, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>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 Diseases, Department of Clinical Haematology, Monash University and Alfred Health Alfred Centre, 99 Commercial Road, Melbourne, Victoria 3004</wicri:regionArea>
</affiliation>
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<series><title level="j">Nature communications</title>
<idno type="eISSN">2041-1723</idno>
<imprint><date when="2015" type="published">2015</date>
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<term>Blotting, Western</term>
<term>Chromatin Immunoprecipitation</term>
<term>Flow Cytometry</term>
<term>Gene Expression Profiling</term>
<term>Gene Expression Regulation, Neoplastic (genetics)</term>
<term>Gene Expression Regulation, Neoplastic (physiology)</term>
<term>Histological Techniques</term>
<term>Homeodomain Proteins (genetics)</term>
<term>Homeodomain Proteins (immunology)</term>
<term>Humans</term>
<term>Immunohistochemistry</term>
<term>In Situ Hybridization, Fluorescence</term>
<term>Janus Kinases (metabolism)</term>
<term>Kaplan-Meier Estimate</term>
<term>Karyotyping</term>
<term>Leukemia, T-Cell (physiopathology)</term>
<term>Luciferases</term>
<term>Mice</term>
<term>Real-Time Polymerase Chain Reaction</term>
<term>Receptors, Interleukin-7 (metabolism)</term>
<term>Repressor Proteins (genetics)</term>
<term>Repressor Proteins (immunology)</term>
<term>STAT Transcription Factors (metabolism)</term>
<term>Signal Transduction (genetics)</term>
<term>Signal Transduction (physiology)</term>
</keywords>
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<term>Animaux</term>
<term>Caryotypage</term>
<term>Cytométrie en flux</term>
<term>Estimation de Kaplan-Meier</term>
<term>Facteurs de transcription STAT (métabolisme)</term>
<term>Humains</term>
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<term>Régulation de l'expression des gènes tumoraux (physiologie)</term>
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<term>Techniques histologiques</term>
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<term>Transduction du signal (physiologie)</term>
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<front><div type="abstract" xml:lang="en">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.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">25565005</PMID>
<DateCreated><Year>2015</Year>
<Month>01</Month>
<Day>08</Day>
</DateCreated>
<DateCompleted><Year>2015</Year>
<Month>12</Month>
<Day>08</Day>
</DateCompleted>
<DateRevised><Year>2017</Year>
<Month>11</Month>
<Day>16</Day>
</DateRevised>
<Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">2041-1723</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>6</Volume>
<PubDate><Year>2015</Year>
<Month>Jan</Month>
<Day>07</Day>
</PubDate>
</JournalIssue>
<Title>Nature communications</Title>
<ISOAbbreviation>Nat Commun</ISOAbbreviation>
</Journal>
<ArticleTitle>ZEB2 drives immature T-cell lymphoblastic leukaemia development via enhanced tumour-initiating potential and IL-7 receptor signalling.</ArticleTitle>
<Pagination><MedlinePgn>5794</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1038/ncomms6794</ELocationID>
<Abstract><AbstractText>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.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Goossens</LastName>
<ForeName>Steven</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>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-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.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Radaelli</LastName>
<ForeName>Enrico</ForeName>
<Initials>E</Initials>
<AffiliationInfo><Affiliation>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.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Blanchet</LastName>
<ForeName>Odile</ForeName>
<Initials>O</Initials>
<AffiliationInfo><Affiliation>1] Institut Universitaire d'Hématologie and U944 INSERM, Hopital Saint-Louis, Paris 75010, France [2] Department of Hematology and Immunology, CHU, Angers 49100, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Durinck</LastName>
<ForeName>Kaat</ForeName>
<Initials>K</Initials>
<AffiliationInfo><Affiliation>Center for Medical Genetics, Ghent University Hospital, Ghent B-9000, Belgium.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Van der Meulen</LastName>
<ForeName>Joni</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Center for Medical Genetics, Ghent University Hospital, Ghent B-9000, Belgium.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Peirs</LastName>
<ForeName>Sofie</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Center for Medical Genetics, Ghent University Hospital, Ghent B-9000, Belgium.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Taghon</LastName>
<ForeName>Tom</ForeName>
<Initials>T</Initials>
<AffiliationInfo><Affiliation>Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent B-9000, Belgium.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Tremblay</LastName>
<ForeName>Cedric S</ForeName>
<Initials>CS</Initials>
<AffiliationInfo><Affiliation>Stem Cell Research Group, Division of Blood Cancers, Australian Centre for Blood Diseases, Monash University, Melbourne, Victoria 3004, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Costa</LastName>
<ForeName>Magdaline</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>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.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Farhang Ghahremani</LastName>
<ForeName>Morvarid</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>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.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>De Medts</LastName>
<ForeName>Jelle</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent B-9000, Belgium.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Bartunkova</LastName>
<ForeName>Sonia</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Vascular Cell Biology Unit, VIB Inflammation Research Center, Ghent University, Ghent B-9052, Belgium.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Haigh</LastName>
<ForeName>Katharina</ForeName>
<Initials>K</Initials>
<AffiliationInfo><Affiliation>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 Diseases, Department of Clinical Haematology, Monash University and Alfred Health Alfred Centre, 99 Commercial Road, Melbourne, Victoria 3004, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Schwab</LastName>
<ForeName>Claire</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne NE2 4AD, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Farla</LastName>
<ForeName>Natalie</ForeName>
<Initials>N</Initials>
<AffiliationInfo><Affiliation>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-9052, Belgium.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Pieters</LastName>
<ForeName>Tim</ForeName>
<Initials>T</Initials>
<AffiliationInfo><Affiliation>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-9052, Belgium [4] Center for Medical Genetics, Ghent University Hospital, Ghent B-9000, Belgium.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Matthijssens</LastName>
<ForeName>Filip</ForeName>
<Initials>F</Initials>
<AffiliationInfo><Affiliation>Center for Medical Genetics, Ghent University Hospital, Ghent B-9000, Belgium.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Van Roy</LastName>
<ForeName>Nadine</ForeName>
<Initials>N</Initials>
<AffiliationInfo><Affiliation>Center for Medical Genetics, Ghent University Hospital, Ghent B-9000, Belgium.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Best</LastName>
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	Serveur d'exploration sur les relations entre la France et l'Australie
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Serveur d'exploration sur les relations entre la France et l'Australie

ZEB2 drives immature T-cell lymphoblastic leukaemia development via enhanced tumour-initiating potential and IL-7 receptor signalling.

ZEB2 drives immature T-cell lymphoblastic leukaemia development via enhanced tumour-initiating potential and IL-7 receptor signalling.

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