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


Goossens, S; Radaelli, E; Blanchet, O; Durinck, K; Van der Meulen, J; Peirs, S; Taghon, T; Tremblay, CS; Costa, M; Farhang Ghahremani, M; 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-Barrett, 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, JP; Soulier, J; Van Vlierberghe, P; Haigh, JJ
2015
Nat Commun
Journal Article
6
5794
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.
NPG
Cancer and Haematology
10.1038/ncomms6794
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Creation Date 2015-01-22 11:26:07 Last Modified 2015-05-20 02:28:56