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

S Goossens; E Radaelli; O Blanchet; K Durinck; J van der Meulen; S Peirs; T Taghon; CS Tremblay; M (Marco) Costa; MF Ghahremani; J De Medts; S Bartunkova; K Haigh; C Schwab; N Farla; T Pieters; F Matthijssens; N van Roy; JA Best; K Deswarte; P Bogaert; C Carmichael; A Rickard; S Suryani; LS Bracken; R Alserihi; Kirsten Canté; L Haenebalcke; E Clappier; P Rondou; K Slowicka; Danny Huylebroeck; AW Goldrath; V Janzen; MP McCormack; RB Lock; DJ Curtis; C Harrison; G Berx; F Speleman; Jules Meijerink; J Soulier; P van Vlierberghe; JJ Haigh

doi:10.1038/ncomms6794

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

S Goossens, E Radaelli, O Blanchet, K Durinck, J van der Meulen, S Peirs, T Taghon, CS Tremblay, M (Marco) Costa, MF Ghahremani, J De Medts, S Bartunkova, K Haigh, C Schwab, N Farla, T Pieters, F Matthijssens, N van Roy, JA Best, K DeswarteP Bogaert, C Carmichael, A Rickard, S Suryani, LS Bracken, R Alserihi, Kirsten Canté, L Haenebalcke, E Clappier, P Rondou, K Slowicka, Danny Huylebroeck, AW Goldrath, V Janzen, MP McCormack, RB Lock, DJ Curtis, C Harrison, G Berx, F Speleman, Jules Meijerink, J Soulier, P van Vlierberghe, JJ Haigh

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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.

Original language	Undefined/Unknown
Number of pages	12
Journal	Nature Communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms6794
Publication status	Published - 2015

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Goossens, S., Radaelli, E., Blanchet, O., Durinck, K., van der Meulen, J., Peirs, S., Taghon, T., Tremblay, CS., Costa, M., Ghahremani, MF., De Medts, J., Bartunkova, S., Haigh, K., Schwab, C., Farla, N., Pieters, T., Matthijssens, F., van Roy, N., Best, JA., ... Haigh, JJ. (2015). ZEB2 drives immature T-cell lymphoblastic leukaemia development via enhanced tumour-initiating potential and IL-7 receptor signalling. Nature Communications, 6. https://doi.org/10.1038/ncomms6794

@article{dc99232fee71458888b1ca844e62845b,

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

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.",

author = "S Goossens and E Radaelli and O Blanchet and K Durinck and {van der Meulen}, J and S Peirs and T Taghon and CS Tremblay and Costa, {M (Marco)} and MF Ghahremani and {De Medts}, J and S Bartunkova and K Haigh and C Schwab and N Farla and T Pieters and F Matthijssens and {van Roy}, N and JA Best and K Deswarte and P Bogaert and C Carmichael and A Rickard and S Suryani and LS Bracken and R Alserihi and Kirsten Cant{\'e} and L Haenebalcke and E Clappier and P Rondou and K Slowicka and Danny Huylebroeck and AW Goldrath and V Janzen and MP McCormack and RB Lock and DJ Curtis and C Harrison and G Berx and F Speleman and Jules Meijerink and J Soulier and {van Vlierberghe}, P and JJ Haigh",

year = "2015",

doi = "10.1038/ncomms6794",

language = "Undefined/Unknown",

volume = "6",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

Goossens, S, Radaelli, E, Blanchet, O, Durinck, K, van der Meulen, J, Peirs, S, Taghon, T, Tremblay, CS, Costa, M, Ghahremani, MF, 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, Canté, 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, J, Soulier, J, van Vlierberghe, P & Haigh, JJ 2015, 'ZEB2 drives immature T-cell lymphoblastic leukaemia development via enhanced tumour-initiating potential and IL-7 receptor signalling', Nature Communications, vol. 6. https://doi.org/10.1038/ncomms6794

TY - JOUR

T1 - ZEB2 drives immature T-cell lymphoblastic leukaemia development via enhanced tumour-initiating potential and IL-7 receptor signalling

AU - Goossens, S

AU - Radaelli, E

AU - Blanchet, O

AU - Durinck, K

AU - van der Meulen, J

AU - Peirs, S

AU - Taghon, T

AU - Tremblay, CS

AU - Costa, M (Marco)

AU - Ghahremani, MF

AU - De Medts, J

AU - Bartunkova, S

AU - Haigh, K

AU - Schwab, C

AU - Farla, N

AU - Pieters, T

AU - Matthijssens, F

AU - van Roy, N

AU - Best, JA

AU - Deswarte, K

AU - Bogaert, P

AU - Carmichael, C

AU - Rickard, A

AU - Suryani, S

AU - Bracken, LS

AU - Alserihi, R

AU - Canté, Kirsten

AU - Haenebalcke, L

AU - Clappier, E

AU - Rondou, P

AU - Slowicka, K

AU - Huylebroeck, Danny

AU - Goldrath, AW

AU - Janzen, V

AU - McCormack, MP

AU - Lock, RB

AU - Curtis, DJ

AU - Harrison, C

AU - Berx, G

AU - Speleman, F

AU - Meijerink, Jules

AU - Soulier, J

AU - van Vlierberghe, P

AU - Haigh, JJ

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

U2 - 10.1038/ncomms6794

DO - 10.1038/ncomms6794

M3 - Article

SN - 2041-1723

VL - 6

JO - Nature Communications

JF - Nature Communications

ER -