|
| Status |
Public on Jan 26, 2018 |
| Title |
HOXA9 cooperates with activated JAK/STAT signaling to drive leukemia development |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Leukemia is caused by the accumulation of multiple genomic lesions in hematopoietic precursor cells. However, how these events cooperate during oncogenic transformation remains poorly understood. We studied the cooperation between activated JAK3/STAT5 signaling and HOXA9 overexpression, two events identified as significantly co-occuring in T-cell acute lymphoblastic leukemia. Expression of mutant JAK3 and HOXA9 led to a rapid development of leukemia originating from multipotent or lymphoid-committed progenitors, with a significant decrease in disease latency compared to JAK3 or HOXA9 alone. Integrated RNA-seq, ChIP-seq and ATAC-seq revealed that STAT5 and HOXA9 have co-occupancy across the genome resulting in enhanced STAT5 transcriptional activity and ectopic activation of Fos/Jun (AP-1). Our data suggest that oncogenic transcription factors such as HOXA9 provide a fertile ground for specific signaling pathways to thrive, explaining why JAK/STAT pathway mutations accumulate in HOXA9 expressing cells.
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| |
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| Overall design |
RNA-sequencing and ChIPmentation sequencing on mouse thymus samples
ChIPmentation sequencing on xenograft sample
|
| |
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| Contributor(s) |
Demeyer S, de Bock C, Cools J |
| Citation(s) |
29496663 |
| |
| Submission date |
Jan 25, 2018 |
| Last update date |
Mar 27, 2019 |
| Contact name |
Sofie Demeyer |
| E-mail(s) |
sofie.demeyer@kuleuven.vib.be
|
| Organization name |
KULeuven / VIB
|
| Department |
Center for Cancer Biology
|
| Lab |
Laboratory of Molecular Biology of Leukemia
|
| Street address |
Herestraat 49 / bus 912
|
| City |
Leuven |
| ZIP/Postal code |
3000 |
| Country |
Belgium |
| |
|
| Platforms (2) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
|
| Samples (32)
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|
| Relations |
| BioProject |
PRJNA431601 |
| SRA |
SRP131197 |
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