Inhibiting the oncogenic translation program is an effective therapeutic strategy in multiple myeloma
dc.contributor.author | Manier, Salomon | en_US |
dc.contributor.author | Huynh, Daisy | en_US |
dc.contributor.author | Shen, Yu J. | en_US |
dc.contributor.author | Zhou, Jia | en_US |
dc.contributor.author | Yusufzai, Timur | en_US |
dc.contributor.author | Salem, Karma Z. | en_US |
dc.contributor.author | Ebright, Richard Y. | en_US |
dc.contributor.author | Shi, Jiantao | en_US |
dc.contributor.author | Park, Jihye | en_US |
dc.contributor.author | Glavey, Siobhan V. | en_US |
dc.contributor.author | Devine, William G. | en_US |
dc.contributor.author | Liu, Chia-Jen | en_US |
dc.contributor.author | Leleu, Xavier | en_US |
dc.contributor.author | Quesnel, Bruno | en_US |
dc.contributor.author | Roche-Lestienne, Catherine | en_US |
dc.contributor.author | Snyder, John K. | en_US |
dc.contributor.author | Brown, Lauren E. | en_US |
dc.contributor.author | Gray, Nathanael | en_US |
dc.contributor.author | Bradner, James | en_US |
dc.contributor.author | Whitesell, Luke | en_US |
dc.contributor.author | Porco, John A. | en_US |
dc.contributor.author | Ghobrial, Irene M. | en_US |
dc.date.accessioned | 2018-05-11T13:02:37Z | |
dc.date.available | 2018-05-11T13:02:37Z | |
dc.date.issued | 2017-05-10 | |
dc.identifier.citation | Salomon 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.issn | 1946-6234 | |
dc.identifier.issn | 1946-6242 | |
dc.identifier.uri | https://hdl.handle.net/2144/28877 | |
dc.description | Published in final edited form as: Sci Transl Med. 2017 May 10; 9(389). https://doi.org/10.1126/scitranslmed.aal2668. | en_US |
dc.description.abstract | Multiple 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.publisher | American Association for the Advancement of Science (AAAS) | en_US |
dc.relation.ispartof | Science Translational Medicine [19466234] | |
dc.subject | Medical and health sciences | en_US |
dc.subject | Biological sciences | en_US |
dc.title | Inhibiting the oncogenic translation program is an effective therapeutic strategy in multiple myeloma | en_US |
dc.type | Article | en_US |
dc.identifier.doi | 10.1126/SCITRANSLMED.AAL2668 | |
pubs.elements-source | c-inst-1 | en_US |
pubs.notes | Embargo: Not known | en_US |
pubs.organisational-group | Boston University | en_US |
pubs.organisational-group | Boston University, College of Arts & Sciences | en_US |
pubs.organisational-group | Boston University, College of Arts & Sciences, Department of Chemistry | en_US |
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BU Open Access Articles [3664]
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CAS: Chemistry: Scholarly Papers [120]