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| Status |
Public on Oct 27, 2014 |
| Title |
Development of gene expression signatures with lncRNAs for T-cell subsets (CD34+ and CD4+CD8+) |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| 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 |
Gene expression was measured in sorted T-cell subsets of 4 healthy donors.
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| Contributor(s) |
Wallaert A, Durinck K, Van de Walle I, Van Loocke W, Volders P, Mestdagh P, Vandesompele J, Taghon T, Speleman F |
| Citation(s) |
25344525 |
| |
| Submission date |
Sep 29, 2014 |
| Last update date |
Feb 18, 2016 |
| Contact name |
Annelynn Wallaert |
| E-mail(s) |
annelynn.wallaert@ugent.be
|
| Organization name |
UGent
|
| Street address |
De Pintelaan 185
|
| City |
Gent |
| ZIP/Postal code |
9000 |
| Country |
Belgium |
| |
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| Platforms (1) |
| GPL19197 |
Agilent-041648 CMGG Human V1.1 60k [Probe Name Version] |
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| Samples (13)
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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 |
|
| Relations |
| BioProject |
PRJNA262920 |
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