|
| Status |
Public on Apr 05, 2016 |
| Title |
Exploiting Temporal Collateral Sensitivity in Tumor Clonal Evolution |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
In this study, using a murine model of Ph+ acute lymphoblastic leukemia (Ph+ ALL), a combined pharmacological profile and drug selection experimental approach identified distinct stages of tumor clonal evolution with vulnerabilities to sets of small molecules. Through genotypic, phenotypic, signaling, and binding measurements, we identified the mutation V299L in the ABL1 kinase domain as mediator for an on-target ABL1 inhibition and hence the sensitization phenotype. To further rule out any off-target effects, we performed RNA-seq analysis of select derived cell lines. Variant calls suggest that although there were other mutations, the only mutation shared among cell lines with the sensitization phenotype and that went from 0% to 100% variant allele frequency was c.895G>C, leading to BCR-ABL1 V299L. In addition, transcriptional profile does not suggest functional changes in BCR-ABL1 V299L and WT cell lines.
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| |
|
| Overall design |
RNA-seq of parental murine Ph+ acute lymphoblastic leukemia (Ph+ ALL) cell line and derived cell lines (via dose escalating concentrations of dasatinib or DMSO vehicle control).
|
| |
|
| Contributor(s) |
Zhao B, Lauffenburger DA, Hemann MT |
| Citation(s) |
26924578 |
| |
| Submission date |
Sep 10, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Boyang Zhao |
| Organization name |
MIT
|
| Street address |
500 Main Street
|
| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02139 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (10)
|
|
| Relations |
| BioProject |
PRJNA295303 |
| SRA |
SRP063569 |
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