dc.contributor.author | Bhanot, Haymanti | en_US |
dc.contributor.author | Reddy, Mamatha M. | en_US |
dc.contributor.author | Nonami, Atsushi | en_US |
dc.contributor.author | Weisberg, Ellen L. | en_US |
dc.contributor.author | Bonal, Dennis | en_US |
dc.contributor.author | Kirschmeier, Paul T. | en_US |
dc.contributor.author | Salgia, Sabrina | en_US |
dc.contributor.author | Podar, Klaus | en_US |
dc.contributor.author | Galinsky, Ilene | en_US |
dc.contributor.author | Chowdary, Tirumala K. | en_US |
dc.contributor.author | Neuberg, Donna | en_US |
dc.contributor.author | Tonon, Giovanni | en_US |
dc.contributor.author | Stone, Richard M. | en_US |
dc.contributor.author | Asara, John | en_US |
dc.contributor.author | Griffin, James D. | en_US |
dc.contributor.author | Sattler, Martin | en_US |
dc.date.accessioned | 2016-02-01T15:45:44Z | |
dc.date.issued | 2015 | en_US |
dc.identifier.citation | Bhanot, H., M. M. Reddy, A. Nonami, E. L. Weisberg, D. Bonal, P. T. Kirschmeier, S. Salgia, et al. 2015. “Pathological glycogenesis through glycogen synthase 1 and suppression of excessive AMP kinase activity in myeloid leukemia cells.” Leukemia 29 (7): 1555-1563. doi:10.1038/leu.2015.46. http://dx.doi.org/10.1038/leu.2015.46. | en |
dc.identifier.issn | 0887-6924 | en |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:24983946 | |
dc.description.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 AMPK (AMP kinase), 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. | en |
dc.language.iso | en_US | en |
dc.relation.isversionof | doi:10.1038/leu.2015.46 | en |
dc.relation.hasversion | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4497855/pdf/ | en |
dash.license | LAA | en_US |
dc.subject | CML | en |
dc.subject | AML | en |
dc.subject | metabolic reprogramming | en |
dc.subject | signal transduction | en |
dc.subject | glycogen | en |
dc.title | Pathological glycogenesis through glycogen synthase 1 and suppression of excessive AMP kinase activity in myeloid leukemia cells | en |
dc.type | Journal Article | en_US |
dc.description.version | Version of Record | en |
dc.relation.journal | Leukemia | en |
dash.depositing.author | Bhanot, Haymanti | en_US |
dc.date.available | 2016-02-01T15:45:44Z | |
dc.identifier.doi | 10.1038/leu.2015.46 | * |
dash.authorsordered | false | |
dash.contributor.affiliated | Bhanot, Haymanti | |
dash.contributor.affiliated | Griffin, James | |
dash.contributor.affiliated | Weisberg, Ellen | |
dash.contributor.affiliated | Sattler, Martin | |
dash.contributor.affiliated | Asara, John | |
dash.contributor.affiliated | Stone, Richard | |