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dc.contributor.authorBhanot, Haymantien_US
dc.contributor.authorReddy, Mamatha M.en_US
dc.contributor.authorNonami, Atsushien_US
dc.contributor.authorWeisberg, Ellen L.en_US
dc.contributor.authorBonal, Dennisen_US
dc.contributor.authorKirschmeier, Paul T.en_US
dc.contributor.authorSalgia, Sabrinaen_US
dc.contributor.authorPodar, Klausen_US
dc.contributor.authorGalinsky, Ileneen_US
dc.contributor.authorChowdary, Tirumala K.en_US
dc.contributor.authorNeuberg, Donnaen_US
dc.contributor.authorTonon, Giovannien_US
dc.contributor.authorStone, Richard M.en_US
dc.contributor.authorAsara, Johnen_US
dc.contributor.authorGriffin, James D.en_US
dc.contributor.authorSattler, Martinen_US
dc.date.accessioned2016-02-01T15:45:44Z
dc.date.issued2015en_US
dc.identifier.citationBhanot, 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.issn0887-6924en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:24983946
dc.description.abstractThe 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.isoen_USen
dc.relation.isversionofdoi:10.1038/leu.2015.46en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4497855/pdf/en
dash.licenseLAAen_US
dc.subjectCMLen
dc.subjectAMLen
dc.subjectmetabolic reprogrammingen
dc.subjectsignal transductionen
dc.subjectglycogenen
dc.titlePathological glycogenesis through glycogen synthase 1 and suppression of excessive AMP kinase activity in myeloid leukemia cellsen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalLeukemiaen
dash.depositing.authorBhanot, Haymantien_US
dc.date.available2016-02-01T15:45:44Z
dc.identifier.doi10.1038/leu.2015.46*
dash.authorsorderedfalse
dash.contributor.affiliatedBhanot, Haymanti
dash.contributor.affiliatedGriffin, James
dash.contributor.affiliatedWeisberg, Ellen
dash.contributor.affiliatedSattler, Martin
dash.contributor.affiliatedAsara, John
dash.contributor.affiliatedStone, Richard


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