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

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

doi:10.1038/ncomms6794

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

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

Steven Goossens, Enrico Radaelli, Odile Blanchet, Kaat Durinck, Joni Van der Meulen, Sofie Peirs, Tom Taghon, Cedric S. Tremblay, Magdaline Costa, Morvarid Farhang Ghahremani, …

Nature communications, Vol.6(1), pp.5794-5794

07/01/2015

DOI: https://doi.org/10.1038/ncomms6794

PMCID: PMC4354161

PMID: 25565005

Abstract

Multidisciplinary Sciences

Science & Technology

Science & Technology - Other Topics

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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Title: ZEB2 drives immature T-cell lymphoblastic leukaemia development via enhanced tumour-initiating potential and IL-7 receptor signalling
Creators - without role: Steven Goossens - VIB-UGent Center for Inflammation Research
Enrico Radaelli - University of Milan
Odile Blanchet - Hôpital Saint-Louis
Kaat Durinck - Ghent University Hospital
Joni Van der Meulen - Ghent University Hospital
Sofie Peirs - Ghent University Hospital
Tom Taghon - Ghent University
Cedric S. Tremblay - Monash University
Magdaline Costa - Alfred Health
Morvarid Farhang Ghahremani - VIB-UGent Center for Inflammation Research
Jelle De Medts - Ghent University
Sonia Bartunkova - VIB-UGent Center for Inflammation Research
Katharina Haigh - VIB-UGent Center for Inflammation Research
Claire Schwab - Newcastle University
Natalie Farla - VIB-UGent Center for Inflammation Research
Tim Pieters - VIB-UGent Center for Inflammation Research
Filip Matthijssens - Ghent University Hospital
Nadine Van Roy - Ghent University Hospital
J. Adam Best - University of California, San Diego
Kim Deswarte - VIB-UGent Center for Inflammation Research
Pieter Bogaert - Ghent University
Catherine Carmichael - Alfred Health
Adam Rickard - Alfred Health
Santi Suryani - UNSW Sydney
Lauryn S. Bracken - UNSW Sydney
Raed Alserihi - Walter and Eliza Hall Institute of Medical Research
Kirsten Cante-Barret - Erasmus MC
Lieven Haenebalcke - VIB-UGent Center for Inflammation Research
Emmanuelle Clappier - Hôpital Saint-Louis
Pieter Rondou - Ghent University Hospital
Karolina Slowicka - VIB-UGent Center for Inflammation Research
Danny Huylebroeck - KU Leuven
Ananda W. Goldrath - University of California, San Diego
Viktor Janzen - University of Bonn
Matthew P. McCormack - Walter and Eliza Hall Institute of Medical Research
Richard B. Lock - UNSW Sydney
David J. Curtis - Monash University
Christine Harrison - Newcastle University
Geert Berx - Ghent University
Frank Speleman - Centre Hospitalier Universitaire d'Angers
Jules P. P. Meijerink - Erasmus MC - Sophia Children’s Hospital
Jean Soulier - Hôpital Saint-Louis
Pieter Van Vlierberghe - Ghent University Hospital
Jody J. Haigh - Ghent University
Publication Details: Nature communications, Vol.6(1), pp.5794-5794
Publisher: Springer Nature
Number of pages: 12
Grant note: Ligue Contre le Cancer grant programme Carte d'Identite des tumeurs (CIT) 311660-CEVAL / ERC St-Grant Consolidator 2009/26 / European Hematology Association (EHA) KIKA2008-029 / Children Cancer Free Foundation (Stichting Kinderen Kankervrij) SLI programme from the French Agence National pour la Recherche Odysseus type II grant Agency for Innovation by Science and Technology (IWT); Institute for the Promotion of Innovation by Science and Technology in Flanders (IWT) R01AI067545 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) Belgian Federation for the Study Against Cancer (BFAC) Royal Dutch Academy of Arts and Sciences FWO-V; FWO G056813N; 3G002711 / Fund for Scientific Research-Flanders (FWO-V); FWO 1047995 / Australian NHMRC grant; National Health and Medical Research Council (NHMRC) of Australia
Identifiers: 9940675508331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article