|
| Status |
Public on Nov 16, 2014 |
| Title |
NRASG12V mediates leukemia self renewal [RNA-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Mutant RAS oncoproteins activate signaling molecules that drive oncogenesis in multiple human tumors including acute myelogenous leukemia (AML). However, the specific function of these pathways in AML is unclear. To elucidate the downstream functions of activated NRAS in AML, we employed a murine model of AML harboring Mll-AF9 and NRASG12V. We found that NRASG12V enforced leukemia self-renewal gene expression signatures and was required to maintain an MLL-AF9 and MYB-dependent gene expression program. In a multiplexed analysis of RAS-dependent signaling intermediates, the leukemia stem cell compartment was preferentially sensitive to RAS withdrawal. Use of RAS-pathway inhibitors showed that NRASG12V maintained leukemia self-renewal through mTOR and MEK pathway activation, implicating these pathways as potential targets for cancer stem cell-specific therapies.
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| Overall design |
Mice harboring NRASG12V/Mll-AF9 AML were treated with doxycyline to abolish NRASG12V expression. Leukemia samples were harvested at 24 hour intervals after doxycyline treatment.
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| Contributor(s) |
Sachs Z, LaRue RS, Nguyen HT, Sachs K, Hassan NA, Diaz-Flores E, Rathe SK, Sarver AL, Bendall SC, Ha NA, Diers MD, Nolan GP, Shannon KM, Largaespada DA |
| Citation(s) |
25316678 |
| |
| Submission date |
Jul 22, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
Rebecca LaRue |
| E-mail(s) |
larue005@umn.edu
|
| Phone |
612-624-0532
|
| Organization name |
University of Minnesota
|
| Department |
Department of Lab medicine and Pathology
|
| Lab |
Minnesota Supercomputing Institute
|
| Street address |
117 Pleasant St SE
|
| City |
Minneapolis |
| State/province |
MN |
| ZIP/Postal code |
55455 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
|
| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE49089 |
NRASG12V oncogene mediates self-renewal in acute myelogenous leukemia |
|
| Relations |
| BioProject |
PRJNA212986 |
| SRA |
SRP028125 |
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