|
| Status |
Public on Jul 23, 2018 |
| Title |
MEF2C phosphorylation is required for chemotherapy resistance in acute myeloid leukemia [inhibitor MRT199665] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
In acute myeloid leukemia, chemotherapy resistance remains prevalent and poorly understood. Using functional proteomics of patient AML specimens, we identified MEF2C S222 phosphorylation as a specific marker of primary chemoresistance. We found that transgenic Mef2cS222A/S222A mice engineered to block MEF2C phosphorylation exhibited normal hematopoiesis, but were resistant to leukemogenesis induced by MLL-AF9. MEF2C phosphorylation was required for leukemia stem cell maintenance, induced by MARK kinases in cells, and blocked by selective MARK inhibitor MRT199665, which caused apoptosis of MEF2C-activated human AML cell lines and primary patient specimens, but not those lacking MEF2C. These findings identify signaling-dependent dysregulation of transcription factor control as a determinant of therapy response in AML, with immediate potential for improved diagnosis and therapy for this disease.
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| |
|
| Overall design |
RNA-sequencing of human leukemia cell line with treatment of MARK inhibitor MRT199665.
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| |
|
| Contributor(s) |
Brown FC, Koche RP, Kentsis A |
| Citation(s) |
29431698 |
| |
| Submission date |
Nov 17, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Richard Koche |
| E-mail(s) |
kocher@mskcc.org
|
| Organization name |
Memorial Sloan Kettering Cancer Center
|
| Street address |
417 E. 68th St.
|
| City |
New York |
| State/province |
New York |
| ZIP/Postal code |
10065 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
|
| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE107073 |
MEF2C phosphorylation is required for chemotherapy resistance in acute myeloid leukemia |
|
| Relations |
| BioProject |
PRJNA418960 |
| SRA |
SRP125208 |
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