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| Status |
Public on Jan 13, 2021 |
| Title |
A genome-wide CRISPR/Cas9 screen in acute myeloid leukemia cells identifies regulators of TAK-243 sensitivity |
| Organism |
Homo sapiens |
| Experiment type |
Other
|
| Summary |
TAK-243 is a first-in-class inhibitor of ubiquitin-like modifier activating enzyme 1 (UBA1) that catalyzes ubiquitin activation, the first step in the ubiquitylation cascade. Based on its preclinical efficacy and tolerability, TAK-243 has been advanced to phase 1 clinical trials in advanced malignancies. Nonetheless, the determinants of TAK-243 sensitivity remain largely unknown. Here, we conducted a genome-wide CRISPR/Cas9 knockout screen in acute myeloid leukemia (AML) cells in the presence of TAK-243 to identify genes essential for TAK-243 action. We identified BEN domain-containing protein 3 (BEND3), a transcriptional repressor and a regulator of chromatin organization, as the top gene whose knockout confers resistance to TAK-243
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| Overall design |
A positive-selection genome-wide CRISPR/Cas9 knockout screen in OCI-AML2 cells to identify gRNAs significantly enriched in the presence of TAK-243. Specifically, cells were treated with DMSO or TAK-243 at 25 nM or 30 nM for 32 days or 36 days, followed by extraction of genomic DNA and sequencing
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| Contributor(s) |
Schimmer AD, Barghout SH |
| Citation(s) |
33476303 |
| |
| Submission date |
Jan 12, 2021 |
| Last update date |
Feb 11, 2021 |
| Contact name |
Aaron D Schimmer |
| E-mail(s) |
aaron.schimmer@uhn.ca
|
| Organization name |
University Health Network
|
| Department |
Princess Margaret Cancer Centre
|
| Lab |
Schimmer Lab
|
| Street address |
101 College Street
|
| City |
Toronto |
| State/province |
ON |
| ZIP/Postal code |
M5G 1L7 |
| Country |
Canada |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (18)
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| Relations |
| BioProject |
PRJNA691473 |
| SRA |
SRP301381 |
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