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dc.contributor.authorvan Dijk, Marianne
dc.contributor.authorMurphy, Eoin
dc.contributor.authorMorrell, Ruth
dc.contributor.authorO'Dwyer, Michael
dc.contributor.authorSzegezd, Eva
dc.contributor.authorSamali, Afshin
dc.date.accessioned2012-02-17T17:26:33Z
dc.date.available2012-02-17T17:26:33Z
dc.date.issued2011
dc.identifier.citationvan Dijk M, Murphy E, Morrell M , Knapper S , O'Dwyer M, Samali A, Eva Szegezdi E. (2011) 'The Proteasome Inhibitor Bortezomib Sensitizes AML with Myelomonocytic Differentiation to TRAIL Mediated Apoptosis'. Cancers, 3 :1329-1350.en_US
dc.identifier.urihttp://hdl.handle.net/10379/2585
dc.description.abstractAcute myeloid leukemia (AML) is an aggressive stem cell malignancy that is difficult to treat. There are limitations to the current treatment regimes especially after disease relapse, and therefore new therapeutic agents are urgently required which can overcome drug resistance whilst avoiding unnecessary toxicity. Among newer targeted agents, both tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and proteasome inhibitors show particular promise. In this report we show that a combination of the proteasome inhibitor bortezomib and TRAIL is effective against AML cell lines, in particular, AML cell lines displaying myelomonocytic/monocytic phenotype (M4/M5 AML based on FAB classification), which account for 20-30% of AML cases. We show that the underlying mechanism of sensitization is at least in part due to bortezomib mediated downregulation of c-FLIP and XIAP, which is likely to be regulated by NF-kB. Blockage of NF-kB activation with BMS-345541 equally sensitized myelomonocytic AML cell lines and primary AML blasts to TRAIL.en_US
dc.description.sponsorshipSFIen_US
dc.formatapplication/pdfen_US
dc.language.isoenen_US
dc.relation.ispartofCancersen
dc.subjectAMLen_US
dc.subjectFAB M4/M5en_US
dc.subjectTRAILen_US
dc.subjectBortezomiben_US
dc.subjectApoptosisen_US
dc.subjectc-FLIPen_US
dc.titleThe Proteasome Inhibitor Bortezomib Sensitizes AML with Myelomonocytic Differentiation to TRAIL Mediated Apoptosisen_US
dc.typeArticleen_US
dc.date.updated2012-02-16T15:13:12Z
dc.local.publishedsourcehttp://www.mdpi.com/2072-6694/3/1/1329/en_US
dc.description.peer-reviewedpeer-reviewed
dc.contributor.funder|~|
dc.internal.rssid1169405
dc.local.contactEva Erzsebet Szegezdi, Biochemistry, Arts/Science Building, Nui Galway. 5038 / 5037 Email: eva.szegezdi@nuigalway.ie
dc.local.copyrightcheckedNo
dc.local.versionPUBLISHED
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