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dc.contributor.authorManier, Salomonen_US
dc.contributor.authorHuynh, Daisyen_US
dc.contributor.authorShen, Yu J.en_US
dc.contributor.authorZhou, Jiaen_US
dc.contributor.authorYusufzai, Timuren_US
dc.contributor.authorSalem, Karma Z.en_US
dc.contributor.authorEbright, Richard Y.en_US
dc.contributor.authorShi, Jiantaoen_US
dc.contributor.authorPark, Jihyeen_US
dc.contributor.authorGlavey, Siobhan V.en_US
dc.contributor.authorDevine, William G.en_US
dc.contributor.authorLiu, Chia-Jenen_US
dc.contributor.authorLeleu, Xavieren_US
dc.contributor.authorQuesnel, Brunoen_US
dc.contributor.authorRoche-Lestienne, Catherineen_US
dc.contributor.authorSnyder, John K.en_US
dc.contributor.authorBrown, Lauren E.en_US
dc.contributor.authorGray, Nathanaelen_US
dc.contributor.authorBradner, Jamesen_US
dc.contributor.authorWhitesell, Lukeen_US
dc.contributor.authorPorco, John A.en_US
dc.contributor.authorGhobrial, Irene M.en_US
dc.date.accessioned2018-05-11T13:02:37Z
dc.date.available2018-05-11T13:02:37Z
dc.date.issued2017-05-10
dc.identifier.citationSalomon Manier, Daisy Huynh, Yu J Shen, Jia Zhou, Timur Yusufzai, Karma Z Salem, Richard Y Ebright, Jiantao Shi, Jihye Park, Siobhan V Glavey, William G Devine, Chia-Jen Liu, Xavier Leleu, Bruno Quesnel, Catherine Roche-Lestienne, John K Snyder, Lauren E Brown, Nathanael Gray, James Bradner, Luke Whitesell, John A Porco, Irene M Ghobrial. 2017. "Inhibiting the oncogenic translation program is an effective therapeutic strategy in multiple myeloma." Science Translational Medicine [19466234], Volume 9, Issue 389,
dc.identifier.issn1946-6234
dc.identifier.issn1946-6242
dc.identifier.urihttps://hdl.handle.net/2144/28877
dc.descriptionPublished in final edited form as: Sci Transl Med. 2017 May 10; 9(389). https://doi.org/10.1126/scitranslmed.aal2668.en_US
dc.description.abstractMultiple myeloma (MM) is a frequently incurable hematological cancer in which overactivity of MYC plays a central role, notably through up-regulation of ribosome biogenesis and translation. To better understand the oncogenic program driven by MYC and investigate its potential as a therapeutic target, we screened a chemically diverse small-molecule library for anti-MM activity. The most potent hits identified were rocaglate scaffold inhibitors of translation initiation. Expression profiling of MM cells revealed reversion of the oncogenic MYC-driven transcriptional program by CMLD010509, the most promising rocaglate. Proteome-wide reversion correlated with selective depletion of short-lived proteins that are key to MM growth and survival, most notably MYC, MDM2, CCND1, MAF, and MCL-1. The efficacy of CMLD010509 in mouse models of MM confirmed the therapeutic relevance of these findings in vivo and supports the feasibility of targeting the oncogenic MYC-driven translation program in MM with rocaglates.en_US
dc.publisherAmerican Association for the Advancement of Science (AAAS)en_US
dc.relation.ispartofScience Translational Medicine [19466234]
dc.subjectMedical and health sciencesen_US
dc.subjectBiological sciencesen_US
dc.titleInhibiting the oncogenic translation program is an effective therapeutic strategy in multiple myelomaen_US
dc.typeArticleen_US
dc.identifier.doi10.1126/SCITRANSLMED.AAL2668
pubs.elements-sourcec-inst-1en_US
pubs.notesEmbargo: Not knownen_US
pubs.organisational-groupBoston Universityen_US
pubs.organisational-groupBoston University, College of Arts & Sciencesen_US
pubs.organisational-groupBoston University, College of Arts & Sciences, Department of Chemistryen_US


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