Back to Search
Start Over
Pathological glycogenesis through glycogen synthase 1 and suppression of excessive AMP kinase activity in myeloid leukemia cells.
- Source :
- Leukemia (08876924); Jul2015, Vol. 29 Issue 7, p1555-1563, 9p, 5 Graphs
- Publication Year :
- 2015
-
Abstract
- The rapid proliferation of myeloid leukemia cells is highly dependent on increased glucose metabolism. Through an unbiased metabolomics analysis of leukemia cells, we found that the glycogenic precursor UDP-D-glucose is pervasively upregulated, despite low glycogen levels. Targeting the rate-limiting glycogen synthase 1 (GYS1) not only decreased glycolytic flux but also increased activation of the glycogen-responsive AMP kinase (AMPK), leading to significant growth suppression. Further, genetic and pharmacological hyper-activation of AMPK was sufficient to induce the changes observed with GYS1 targeting. Cancer genomics data also indicate that elevated levels of the glycogenic enzymes GYS1/2 or GBE1 (glycogen branching enzyme 1) are associated with poor survival in AML. These results suggest a novel mechanism whereby leukemic cells sustain aberrant proliferation by suppressing excess AMPK activity through elevated glycogenic flux and provide a therapeutic entry point for targeting leukemia cell metabolism. [ABSTRACT FROM AUTHOR]
- Subjects :
- MYELOID leukemia
GLUCOSE metabolism
GLYCOGEN synthases
LEUKEMIA
GENOMICS
ANIMALS
APOPTOSIS
BIOCHEMISTRY
CELL physiology
EPITHELIAL cells
FLOW cytometry
GLYCOGEN
GLYCOLYSIS
MICE
PHOSPHORYLATION
PHOSPHOTRANSFERASES
POLYMERASE chain reaction
PROGNOSIS
RNA
SURVIVAL
TRANSFERASES
CASE-control method
REVERSE transcriptase polymerase chain reaction
CANCER cell culture
Subjects
Details
- Language :
- English
- ISSN :
- 08876924
- Volume :
- 29
- Issue :
- 7
- Database :
- Complementary Index
- Journal :
- Leukemia (08876924)
- Publication Type :
- Academic Journal
- Accession number :
- 103702262
- Full Text :
- https://doi.org/10.1038/leu.2015.46