Fli-1 overexpression in hematopoietic progenitors deregulates T cell development and induces pre-T cell lymphoblastic leukaemia/lymphoma

Monique F M A Smeets, Angela C Y Chan, Samantha Dagger, Cara Bradley, Andrew Wei, David J Izon

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The Ets transcription factor Fli-1 is preferentially expressed in hematopoietic tissues and cells, including immature T cells, but the role of Fli-1 in T cell development has not been closely examined. To address this we retrovirally overexpressed Fli-1 in various in vitro and in vivo settings and analysed its effect on T cell development. We found that Fli-1 overexpression perturbed the DN to DP transition and inhibited CD4 development whilst enhancing CD8 development both in vitro and in vivo. Surprisingly, Fli-1 overexpression in vivo eventuated in development of pre-T cell lymphoblastic leukaemia/lymphoma (pre-T LBL). Known Fli-1 target genes such as the pro-survival Bcl-2 family members were not found to be upregulated. In contrast, we found increased NOTCH1 expression in all Fli-1 T cells and detected Notch1 mutations in all tumours. These data show a novel function for Fli-1 in T cell development and leukaemogenesis and provide a new mouse model of pre-T LBL to identify treatment options that target the Fli-1 and Notch1 signalling pathways. ? 2013 Smeets et al.
Original languageEnglish
Article numbere62346
Number of pages12
JournalPLoS ONE
Volume8
Issue number5
DOIs
Publication statusPublished - 2013

Cite this

Smeets, Monique F M A ; Chan, Angela C Y ; Dagger, Samantha ; Bradley, Cara ; Wei, Andrew ; Izon, David J. / Fli-1 overexpression in hematopoietic progenitors deregulates T cell development and induces pre-T cell lymphoblastic leukaemia/lymphoma. In: PLoS ONE. 2013 ; Vol. 8, No. 5.
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abstract = "The Ets transcription factor Fli-1 is preferentially expressed in hematopoietic tissues and cells, including immature T cells, but the role of Fli-1 in T cell development has not been closely examined. To address this we retrovirally overexpressed Fli-1 in various in vitro and in vivo settings and analysed its effect on T cell development. We found that Fli-1 overexpression perturbed the DN to DP transition and inhibited CD4 development whilst enhancing CD8 development both in vitro and in vivo. Surprisingly, Fli-1 overexpression in vivo eventuated in development of pre-T cell lymphoblastic leukaemia/lymphoma (pre-T LBL). Known Fli-1 target genes such as the pro-survival Bcl-2 family members were not found to be upregulated. In contrast, we found increased NOTCH1 expression in all Fli-1 T cells and detected Notch1 mutations in all tumours. These data show a novel function for Fli-1 in T cell development and leukaemogenesis and provide a new mouse model of pre-T LBL to identify treatment options that target the Fli-1 and Notch1 signalling pathways. ? 2013 Smeets et al.",
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Fli-1 overexpression in hematopoietic progenitors deregulates T cell development and induces pre-T cell lymphoblastic leukaemia/lymphoma. / Smeets, Monique F M A; Chan, Angela C Y; Dagger, Samantha; Bradley, Cara; Wei, Andrew; Izon, David J.

In: PLoS ONE, Vol. 8, No. 5, e62346, 2013.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Wei, Andrew

AU - Izon, David J

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