| Literature DB >> 25565005 |
Steven Goossens1, Enrico Radaelli2, Odile Blanchet3, Kaat Durinck4, Joni Van der Meulen4, Sofie Peirs4, Tom Taghon5, Cedric S Tremblay6, Magdaline Costa7, Morvarid Farhang Ghahremani8, Jelle De Medts5, Sonia Bartunkova9, Katharina Haigh10, Claire Schwab11, Natalie Farla12, Tim Pieters13, Filip Matthijssens4, Nadine Van Roy4, J Adam Best14, Kim Deswarte15, Pieter Bogaert16, Catherine Carmichael7, Adam Rickard7, Santi Suryani17, Lauryn S Bracken17, Raed Alserihi18, Kirsten Canté-Barrett19, Lieven Haenebalcke8, Emmanuelle Clappier3, Pieter Rondou4, Karolina Slowicka8, Danny Huylebroeck20, Ananda W Goldrath14, Viktor Janzen21, Matthew P McCormack18, Richard B Lock17, David J Curtis6, Christine Harrison11, Geert Berx22, Frank Speleman23, Jules P P Meijerink19, Jean Soulier3, Pieter Van Vlierberghe4, Jody J Haigh10.
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.Entities:
Mesh：
Substances：
Year: 2015 PMID： 25565005 PMCID： PMC4354161 DOI： 10.1038/ncomms6794
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 17.694