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The Proteasome Inhibitor Bortezomib Sensitizes AML with Myelomonocytic Differentiation to TRAIL Mediated Apoptosis

ARAN - Access to Research at NUI Galway

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dc.contributor.author van Dijk, Marianne
dc.contributor.author Murphy, Eoin
dc.contributor.author Morrell, Ruth
dc.contributor.author O'Dwyer, Michael
dc.contributor.author Szegezd, Eva
dc.contributor.author Samali, Afshin
dc.date.accessioned 2012-02-17T17:26:33Z
dc.date.available 2012-02-17T17:26:33Z
dc.date.issued 2011
dc.identifier.citation van 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.uri http://hdl.handle.net/10379/2585
dc.description.abstract Acute 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.sponsorship SFI en_US
dc.format application/pdf en_US
dc.language.iso en en_US
dc.relation.ispartof Cancers en
dc.subject AML en_US
dc.subject FAB M4/M5 en_US
dc.subject TRAIL en_US
dc.subject Bortezomib en_US
dc.subject Apoptosis en_US
dc.subject c-FLIP en_US
dc.title The Proteasome Inhibitor Bortezomib Sensitizes AML with Myelomonocytic Differentiation to TRAIL Mediated Apoptosis en_US
dc.type Article en_US
dc.date.updated 2012-02-16T15:13:12Z
dc.local.publishedsource http://www.mdpi.com/2072-6694/3/1/1329/ en_US
dc.description.peer-reviewed peer-reviewed
dc.contributor.funder |~|
dc.internal.rssid 1169405
dc.local.contact Eva Erzsebet Szegezdi, Biochemistry, Arts/Science Building, Nui Galway. 5038 / 5037 Email: eva.szegezdi@nuigalway.ie
dc.local.copyrightchecked No
dc.local.version PUBLISHED

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