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| Status |
Public on May 23, 2015 |
| Title |
Gene expression profiling of P53/R26 +/+ (n=2) versus P53/R26-Zeb2tg/tg (n=3) thymic tumors |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Early T-cell precursor leukemia (ETP-ALL) is a high-risk subtype of human leukemia that is poorly understood at the molecular level. Here, we report translocations targeting the zinc finger E-box binding transcription factor ZEB2 as a new and recurrent genetic lesion in immature/ETP-ALL. Using a conditional gain-of-function mouse model, we demonstrate that sustained Zeb2 expression perturbs normal T-cell differentiation and initiates T-cell leukemia. Moreover, Zeb2 driven mouse leukemia exhibit some features of the human immature/ETPALL gene expression signature, as well as an enhanced leukemia-initiation potential and activated JAK/STAT signaling through transcriptional activation of IL7R. This study reveals ZEB2 as a novel 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.
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| Overall design |
Conditional Zeb2 knockin mouse model was developed and crossed into p53 null background. Murine T-cell leukemia/lymphoma tumors developed both in the p53 null control and the p53 null Zeb2 transgenic group. In this experiment, gene expression profiling was performed on these murine leukemias to determine the transcriptional program associated with sustained Zeb2 expression in the context of P53 null driven murine T cell leukemogenesis.
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| Contributor(s) |
Goossens S, Van Vlierberghe P, Van der Meulen J, Durinck K, Haigh J |
| Citation(s) |
25565005 |
| Submission date |
Oct 23, 2014 |
| Last update date |
Feb 02, 2018 |
| Contact name |
Kaat Durinck |
| E-mail(s) |
kaat.durinck@ugent.be
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| Phone |
003293322453
|
| Organization name |
Center for Medical Genetics
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| Department |
Biomolecular Medicine
|
| Street address |
Corneel Heymanslaan 10
|
| City |
Ghent |
| ZIP/Postal code |
9000 |
| Country |
Belgium |
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| Platforms (1) |
| GPL10787 |
Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Probe Name version) |
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| Samples (5)
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| Relations |
| BioProject |
PRJNA264722 |
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