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| Status |
Public on Oct 27, 2014 |
| Title |
RNA-sequencing of the GSI treatment of the CUTLL1 cell line |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Genetic studies in T-cell acute lymphoblastic leukemia have uncovered a remarkable complexity of oncogenic and loss-of-function mutations. Amongst this plethora of genetic changes, NOTCH1 activating mutations stand out as the most frequently occurring genetic defect, identified in more than 50% of T-cell acute lymphoblastic leukemias, supporting an essential driver role for this gene in T-cell acute lymphoblastic leukemia oncogenesis. In this study, we aimed to establish a comprehensive compendium of the long non-coding RNA transcriptome under control of Notch signaling. For this purpose, we measured the transcriptional response of all protein coding genes and long non-coding RNAs upon pharmacological Notch inhibition in the human T-cell acute lymphoblastic leukemia cell line CUTLL1 using RNA-sequencing. Similar Notch dependent profiles were established for normal human CD34+ thymic T-cell progenitors exposed to Notch signaling activity in vivo. In addition, we generated long non-coding RNA expression profiles (array data) from GSI treated T-ALL cell lines, ex vivo isolated Notch active CD34+ and Notch inactive CD4+CD8+ thymocytes and from a primary cohort of 15 T-cell acute lymphoblastic leukemia patients with known NOTCH1 mutation status. Integration of these expression datasets with publically available Notch1 ChIP-sequencing data resulted in the identification of long non-coding RNAs directly regulated by Notch activity in normal and malignant T-cell context. Given the central role of Notch in T-cell acute lymphoblastic leukemia oncogenesis, these data pave the way towards development of novel therapeutic strategies that target hyperactive Notch1 signaling in human T-cell acute lymphoblastic leukemia.
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| Overall design |
CUTLL1 cell lines were treated with Compound E (GSI) or DMSO (solvent control). Cells were collected 12 h and 48 h after treatment. This was performed for 3 replicates. RNA-sequencing was performed on these samples.
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| Contributor(s) |
Wallaert A, Durinck K, Van Loocke W, Geerdens E, Cools J, Speleman F |
| Citation(s) |
25344525 |
| |
| Submission date |
Oct 02, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Annelynn Wallaert |
| E-mail(s) |
[email protected]
|
| Organization name |
UGent
|
| Street address |
De Pintelaan 185
|
| City |
Gent |
| ZIP/Postal code |
9000 |
| Country |
Belgium |
| |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE62006 |
The Notch driven long non-coding RNA repertoire in T-cell acute lymphoblastic leukemia |
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| Relations |
| BioProject |
PRJNA262921 |
| SRA |
SRP048603 |
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