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| Status |
Public on Nov 15, 2016 |
| Title |
A Druggable TCF4- and BRD4-dependent Transcriptional Network Sustains Malignancy in Blastic Plasmacytoid Dendritic Cell Neoplasm (RNA-Seq) |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive and largely incurable hematologic malignancy originating from plasmacytoid dendritic cells (pDCs). Using RNA interference screening, we identified the E-box transcription factor TCF4 as a master regulator of the BPDCN oncogenic program. TCF4 served as a faithful diagnostic marker of BPDCN, and its downregulation caused the loss of the BPDCN-specific expression program and apoptosis. High-throughput drug screening revealed that bromodomain and extra-terminal domain inhibitors (BETi's) induce BPDCN apoptosis, which was attributable to disruption of the TCF4-dependent transcriptional network and loss of BPDCN-specific super-enhancers. BETi's retarded the growth of BPDCN xenografts, supporting their clinical evaluation in this recalcitrant malignancy.
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| Overall design |
We performed RNA sequencing (RNA-Seq) on the 6 FFPE BPDCN biopsies for which the FFPE RNA was not excessively degraded. Because only one PHN and none of the primary AML cases passed the RNA QC for library generation, we embedded BPDCN cell lines (Cal-1 and Gen2.2) and AML cell lines (HL-60, MOLM-14 and SKM-1) in paraffin blocks after formalin fixation, and used the FFPE RNA-Seq from these cell lines as a compare/contrast control.
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| Citation(s) |
27846392 |
| Submission date |
Jul 15, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Louis M. Staudt |
| E-mail(s) |
lstaudt@mail.nih.gov
|
| Phone |
301-402-1892
|
| Organization name |
National Cancer Institute
|
| Department |
Lymphoid Malignancies Branch
|
| Lab |
Louis M Staudt
|
| Street address |
9000 Rockville Pike, Bldg 10, Rm 4N114
|
| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (2) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (14)
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| Relations |
| BioProject |
PRJNA329312 |
| SRA |
SRP078597 |
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