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dc.contributor.authorAlharbi, RAen_US
dc.contributor.authorPandha, HSen_US
dc.contributor.authorSimpson, GRen_US
dc.contributor.authorPettengell, Ren_US
dc.contributor.authorPoterlowicz, Ken_US
dc.contributor.authorThompson, Aen_US
dc.contributor.authorHarrington, Ken_US
dc.contributor.authorEl-Tanani, Men_US
dc.contributor.authorMorgan, Ren_US
dc.date.accessioned2018-04-27T11:54:12Z
dc.date.issued2017-10en_US
dc.identifier.citationOncotarget, 2017, 8 (52), pp. 89566 - 89579en_US
dc.identifier.issn1949-2553en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1660
dc.identifier.eissn1949-2553en_US
dc.identifier.doi10.18632/oncotarget.20023en_US
dc.description.abstractThe HOX genes encode a family of transcription factors that have key roles in both development and malignancy. Disrupting the interaction between HOX proteins and their binding partner, PBX, has been shown to cause apoptotic cell death in a range of solid tumors. However, despite HOX proteins playing a particularly significant role in acute myeloid leukemia (AML), the relationship between HOX gene expression and patient survival has not been evaluated (with the exception of HOXA9), and the mechanism by which HOX/PBX inhibition induces cell death in this malignancy is not well understood. In this study, we show that the expression of HOXA5, HOXB2, HOXB4, HOXB9, and HOXC9, but not HOXA9, in primary AML samples is significantly related to survival. Furthermore, the previously described inhibitor of HOX/PBX dimerization, HXR9, is cytotoxic to both AML-derived cell lines and primary AML cells from patients. The mechanism of cell death is not dependent on apoptosis but instead involves a regulated form of necrosis referred to as necroptosis. HXR9-induced necroptosis is enhanced by inhibitors of protein kinase C (PKC) signaling, and HXR9 combined with the PKC inhibitor Ro31 causes a significantly greater reduction in tumor growth compared to either reagent alone.en_US
dc.formatElectronic-eCollectionen_US
dc.format.extent89566 - 89579en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.titleInhibition of HOX/PBX dimer formation leads to necroptosis in acute myeloid leukemia cells.en_US
dc.typeJournal Article
dcterms.dateAccepted2017-06-26en_US
rioxxterms.versionofrecord10.18632/oncotarget.20023en_US
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0en_US
rioxxterms.licenseref.startdate2017-10en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfOncotargeten_US
pubs.issue52en_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Targeted Therapy
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Targeted Therapy
pubs.publication-statusPublisheden_US
pubs.volume8en_US
pubs.embargo.termsNot knownen_US
icr.researchteamTargeted Therapyen_US
dc.contributor.icrauthorHarrington, Kevinen_US


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Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/