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

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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.
Keywords
GENES, SIP1, EXPRESSION, CANCER, MIR-200 FAMILY, OF-FUNCTION MUTATIONS, MICE, PRECURSOR, NOTCH1, GAIN

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Chicago
Goossens, Steven, Enrico Radaelli, Odile Blanchet, Kaat Durinck, Joni Van der Meulen, Sofie Peirs, Tom Taghon, et al. 2015. “ZEB2 Drives Immature T-cell Lymphoblastic Leukaemia Development via Enhanced Tumour-initiating Potential and IL-7 Receptor Signalling.” Nature Communications 6.
APA
Goossens, S., Radaelli, E., Blanchet, O., Durinck, K., Van der Meulen, J., Peirs, S., Taghon, T., et al. (2015). ZEB2 drives immature T-cell lymphoblastic leukaemia development via enhanced tumour-initiating potential and IL-7 receptor signalling. NATURE COMMUNICATIONS, 6.
Vancouver
1.
Goossens S, Radaelli E, Blanchet O, Durinck K, Van der Meulen J, Peirs S, et al. ZEB2 drives immature T-cell lymphoblastic leukaemia development via enhanced tumour-initiating potential and IL-7 receptor signalling. NATURE COMMUNICATIONS. 2015;6.
MLA
Goossens, Steven, Enrico Radaelli, Odile Blanchet, et al. “ZEB2 Drives Immature T-cell Lymphoblastic Leukaemia Development via Enhanced Tumour-initiating Potential and IL-7 Receptor Signalling.” NATURE COMMUNICATIONS 6 (2015): n. pag. Print.
@article{5889715,
  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.},
  articleno    = {5794},
  author       = {Goossens, Steven and Radaelli, Enrico and Blanchet, Odile and Durinck, Kaat and Van der Meulen, Joni and Peirs, Sofie and Taghon, Tom and Tremblay, Cedric S and Costa, Magdaline and Ghahremani, Morvarid Farhang and De Medts, Jelle and Bartunkova, Sona and Haigh, Katharina and Schwab, Claire and Farla, Natalie and Pieters, Tim and Matthijssens, Filip and Van Roy, Nadine and Best, J Adam and Deswarte, Kim and Bogaert, Pieter and Carmichael, Catherine and Rickard, Adam and Suryani, Santi and Bracken, Lauryn S and Alserihi, Raed and Cante-Barret, Kirsten and Haenebalcke, Lieven and Clappier, Emmanuelle and Rondou, Pieter and Slowicka, Karolina and Huylebroeck, Danny and Goldrath, Ananda W and Janzen, Viktor and McCormack, Matthew P and Lock, Richard B and Curtis, David J and Harrison, Christine and Berx, Geert and Speleman, Franki and Meijerink, Jules PP and Soulier, Jean and Van Vlierberghe, Pieter and Haigh, Jody},
  issn         = {2041-1723},
  journal      = {NATURE COMMUNICATIONS},
  language     = {eng},
  pages        = {12},
  title        = {ZEB2 drives immature T-cell lymphoblastic leukaemia development via enhanced tumour-initiating potential and IL-7 receptor signalling},
  url          = {http://dx.doi.org/10.1038/ncomms6794},
  volume       = {6},
  year         = {2015},
}

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