|
| Status |
Public on Sep 05, 2019 |
| Title |
AMPK links acetyl-coA homeostasis to BET recruitment in acute myeloid leukemia: RNA-seq |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Altered metabolism fuels two hallmark properties of cancer cells, unlimited proliferation and differentiation blockade. AMP-activated protein kinase (AMPK) is a master regulator of bioenergetics crucial for glucose metabolism in acute myeloid leukemia (AML) and its inhibition delays leukemogenesis, but whether the metabolic function of AMPK alters AML epigenome remains unknown. Here, we demonstrate that AMPK maintains the epigenome of MLL-rearranged AML by linking acetyl-CoA homeostasis to BET bromodomain protein recruitment to chromatin. AMPK deletion reduced acetyl-CoA and histone acetylation, displacing BET proteins from chromatin in leukemia-initiating cells (LICs). In both mouse and patient-derived xenograft AML models, treating with AMPK and BET inhibitors synergistically suppressed AML. Our results provide a therapeutic rationale to target AMPK and BET for AML therapy.
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| |
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| Overall design |
RNA-seq of sorted AMPK WT or KO leukemia-GMP cells, with three replicates of each.
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| |
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| Contributor(s) |
Jiang Y, Hoegenauer KA, Nakada D |
| Citation missing |
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| |
| Submission date |
Mar 07, 2019 |
| Last update date |
Sep 05, 2019 |
| Contact name |
Daisuke Nakada |
| E-mail(s) |
nakada@bcm.edu
|
| Organization name |
Baylor College of Medicine
|
| Department |
Molecular and Human Genetics
|
| Street address |
One Baylor Plaza
|
| City |
Houston |
| State/province |
Texas |
| ZIP/Postal code |
77030 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE128001 |
AMPK links acetyl-coA homeostasis to BET recruitment in acute myeloid leukemia |
|
| Relations |
| BioProject |
PRJNA526027 |
| SRA |
SRP187857 |
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