Title: ZEB2 drives immature T-cell lymphoblastic leukaemia development via enhanced tumour-initiating potential and IL-7 receptor signalling
Authors: 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 #
Issue Date: 2015
Series Title: Nature Communications vol:6 pages:5794
Article number: 10.1038/ncomms6794
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.
ISSN: 2041-1723
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Stem Cell Biology and Embryology (+)
Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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