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 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 DeswartePieter Bogaert, Catherine Carmichael, Adam Samuel Rickard, Santi Suryani, Lauryn S Bracken, Raed Alserihi, Kirsten Cante-Barrett, Lieven Haenebalcke, Emmanuelle Clappier, Pieter Rondou, Karolina Slowicka, Danny Huylebroeck, Ananda W Goldrath, Viktor Janzen, Matthew McCormack, Richard B Lock, David John Curtis, Christine Harrison, Geert Berx, Frank P Speleman, Jules P P Meijerink, Jean Soulier, Pieter Van Vlierberghe, Jody Jonathan Haigh

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54 Citations (Scopus)


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.
Original languageEnglish
Article number5794
Pages (from-to)1 - 12
Number of pages12
JournalNature Communications
Publication statusPublished - 2015

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