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| Status |
Public on Apr 13, 2018 |
| Title |
Seletive inhibition of CDK9 in DLBCL cell lines |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Deregulation of the MYC transcription factor is a key driver in lymphomagenesis. MYC induces global changes in gene expression that contribute to cell growth, proliferation and oncogenesis by stimulating the activity of RNA polymerases. A key feature in its ability to stimulate RNA Pol II activity is recruitment of pTEFb, an elongation factor whose catalytic core comprises CDK9/cyclin T complexes. Hence, MYC expression and function may be susceptible to CDK9 inhibition. Non-specific inhibitors of multiple CDKs have shown promise in B-cell malignancies, where their pro-apoptotic effect has been attributed to a reduction in transcription and downmodulation of short lived pro-survival proteins (e.g., Mcl-1). However, they lack a defined mechanism of action. Here we selectively targeted CDK9 in a pre-clinical study in DLBCL.
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| Overall design |
We employed gene expression profiling by RNA-Seq to determine which pathways were deregulated by AZ5576, a selective CDK9 inhibitor, in DLBCL cells. VAL cells and OCI-LY3 cells were treated with 0.3 µM AZ-5576 for 3 or 6 hours and comparisons in gene expression were made to vehicle-treated cells. Expression of 30,451 genes was detected in DLBCL cells. Using a cutoff of at least 2-fold change we identified between one and three thousand genes whose expression was significantly affected by AZ5576
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| Contributor(s) |
Hashiguchi T, Danilov AV |
| Citation missing |
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| Submission date |
Apr 12, 2018 |
| Last update date |
Mar 27, 2019 |
| Contact name |
Alexey Danilov |
| Organization name |
Oregon Health and Science Univeristy
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| Street address |
3181 SW Sam Jackson Pk Rd
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| City |
Portland |
| State/province |
OR |
| ZIP/Postal code |
97219 |
| Country |
USA |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA449845 |
| SRA |
SRP139744 |
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