|
| Status |
Public on Apr 01, 2022 |
| Title |
CDK7 inhibition interdicts deregulated transcription and cell cycle control in multiple myeloma [Sensitive_MM_Cell_Lines_RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Cyclin dependent kinases (CDKs) are high value therapeutical targets owing to their important roles in regulating transcription and the cell cycle — two pathways commonly altered in cancer and especially in multiple myeloma (MM). Among CDKs, CDK7 uniquely bridges cell cycle and transcriptional control by activating other cell cycle CDKs and forming the general transcription factor TFIIH. Utilizing a recently developed highly selective covalent inhibitor of CDK7, we demonstrate that CDK7 inhibition elicits a strong therapeutic response in MM blocking proliferation in vitro and driving tumor regression and prolonged survival in vivo. CDK7 inhibition counteracts molecular hallmarks of deregulated cell cycle control at the G1/S checkpoint. Additionally, we show CDK7 inhibition selectively downregulates oncogenic E2F and cell cycle gene expression programs. Combination treatment with JQ1 which target oncogenic enhancer driven gene expression programs proved highly synergistic. These results support CDK7 as an attractive and therapeutically actionable molecular vulnerability in MM.
Cell count normalized RNA-seq in Sensitive MM cell lines (H929 and MM1S; 24 total samples; 3 technical replicates) upon treatment with the selective covalent CDK7 inhibitor YKL-5-124
Mariateresa,Fulciniti
Nikhil,Munshi
|
| |
|
| Overall design |
Charles,Y,Lin
|
| |
|
| Contributor(s) |
Yao Y, Park WD |
| Citation missing |
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| |
| Submission date |
Apr 20, 2021 |
| Last update date |
Apr 02, 2022 |
| Contact name |
Charles Yang Lin |
| E-mail(s) |
charles.y.lin@bcm.edu
|
| Phone |
6172764723
|
| Organization name |
Baylor College of Medicine
|
| Department |
Molecular and Human Genetics
|
| Street address |
1 Baylor Plaza
|
| City |
Houston |
| State/province |
TX |
| ZIP/Postal code |
77030 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
|
| Samples (24)
|
|
| This SubSeries is part of SuperSeries: |
| GSE172445 |
CDK7 inhibition interdicts deregulated transcription and cell cycle control in multiple myeloma |
|
| Relations |
| BioProject |
PRJNA723316 |
| SRA |
SRP315581 |
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