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

Lookup NU author(s): Claire Schwab, Professor Christine Harrison FRCPath FMedSci



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


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.

Publication metadata

Author(s): Goossens S, Radaelli E, Blanchet O, Durinck K, Van der Meulen J, Peirs S, Taghon T, Tremblay CS, Costa M, Ghahremani MF, De Medts J, Bartunkova S, Haigh K, Schwab C, Farla N, Pieters T, Matthijssens F, Van Roy N, Best JA, Deswarte K, Bogaert P, Carmichael C, Rickard A, Suryani S, Bracken LS, Alserihi R, Cante-Barret K, Haenebalcke L, Clappier E, Rondou P, Slowicka K, Huylebroeck D, Goldrath AW, Janzen V, McCormack MP, Lock RB, Curtis DJ, Harrison C, Berx G, Speleman F, Meijerink JPP, Soulier J, Van Vlierberghe P, Haigh JJ

Publication type: Article

Publication status: Published

Journal: Nature Communications

Year: 2015

Volume: 6

Online publication date: 07/01/2015

Acceptance date: 07/11/2014

Date deposited: 09/06/2015

ISSN (electronic): 2041-1723

Publisher: Nature Publishing Group


DOI: 10.1038/ncomms6794


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Funder referenceFunder name
Belgian Federation for the Study Against Cancer (BFAC)
Odysseus type II grant
SLI programme from the French Agence National pour la Recherche
Agency for Innovation by Science and Technology (IWT)
Ligue Contre le Cancer grant programme Carte d'Identite des tumeurs (CIT)
Royal Dutch Academy of Arts and Sciences
1047995Australian NHMRC grant
2009/26European Hematology Association (EHA)
311660-CEVALERC St-Grant Consolidator
3G002711Fund for Scientific Research-Flanders (FWO-V)
G056813NFund for Scientific Research-Flanders (FWO-V)
KIKA2008-029Children Cancer Free Foundation (Stichting Kinderen Kankervrij)