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| Status |
Public on Jun 26, 2018 |
| Title |
Cooperation between TLX1 and the NUP214-ABL1/STAT5 signaling in T-cell acute lymphoblastic leukemia |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
The NUP214-ABL1 fusion is a constitutively activated tyrosine kinase that is significantly associated with overexpression of the TLX1 or TLX3 transcription factors in T-cell acute lymphoblastic (T-ALL). Here we show that NUP214-ABL1 kinase cooperates with TLX1 in driving T-ALL development using a transgenic mouse model. Using ChIP-seq and ATAC-seq, we show that TLX1 and STAT5, the downstream effector of NUP214-ABL1, selectively increase the accessibility of enhancer regions, and cooperatively activate the expression of key proto-oncogenes such as MYC and BCL2. Moreover, MYC is also part of the TLX1/STAT5 complex and inhibition of both MYC and STAT5 leads to reduction of target gene expression.
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| Overall design |
RNA-sequencing of different conditions: wild type, NUP214-ABL1 +, TLX1 +, NUP214-ABL1+TLX1 +, NUP214-ABL1+TLX3 +. Transgenic mouse samples and ALL-SIL cell line. Xenografts of patient samples. Before and after treatment with Imatinib.
ChIPmentation sequencing with different antibodies: STAT5, TLX1, H3K4me3, H3K27ac, p300 and BRD4. Transgenic mouse with NUP214-ABL1+TLX1 +.
ATAC-sequencing for different conditions in mouse: wild type, NUP214-ABL1 +, TLX1 +, NUP214-ABL1+TLX1 +.
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| Contributor(s) |
Demeyer S, Vanden Bempt M, De Bock C, Cools J |
| Citation(s) |
30107177 |
| |
| Submission date |
Aug 03, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Sofie Demeyer |
| E-mail(s) |
sofie.demeyer@kuleuven.vib.be
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| Organization name |
KULeuven / VIB
|
| Department |
Center for Cancer Biology
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| Lab |
Laboratory of Molecular Biology of Leukemia
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| Street address |
Herestraat 49 / bus 912
|
| City |
Leuven |
| ZIP/Postal code |
3000 |
| Country |
Belgium |
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| Platforms (2) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (69)
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| Relations |
| BioProject |
PRJNA397010 |
| SRA |
SRP114758 |
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