dc.contributor.author | Smith, AM | |
dc.contributor.author | Zhang, CRC | |
dc.contributor.author | Cristino, Alexandre | |
dc.contributor.author | Grady, JP | |
dc.contributor.author | Fink, JL | |
dc.contributor.author | Moore, AS | |
dc.date.accessioned | 2020-02-17T01:22:20Z | |
dc.date.available | 2020-02-17T01:22:20Z | |
dc.date.issued | 2019 | |
dc.identifier.issn | 1949-2553 | |
dc.identifier.doi | 10.18632/oncotarget.27206 | |
dc.identifier.uri | http://hdl.handle.net/10072/391549 | |
dc.description.abstract | Kinases such as MEK are attractive targets for novel therapy in cancer, including acute myeloid leukaemia (AML). Acquired and inherent resistance to kinase inhibitors, however, is becoming an increasingly important challenge for the clinical success of such therapeutics, and often arises from mutations in the drug-binding domain of the target kinase. To identify possible causes of resistance to MEK inhibition, we generated a model of resistance by long-term treatment of AML cells with AZD6244 (selumetinib). Remarkably, resistance to MEK inhibition was due to acquired PTEN haploinsufficiency, rather than mutation of MEK. Resistance via this mechanism was confirmed using CRISPR/Cas9 technology targeting exon 5 of PTEN. While PTEN loss has been previously implicated in resistance to a number of other therapeutic agents, this is the first time that it has been shown directly and in AML. | |
dc.description.peerreviewed | Yes | |
dc.language | English | |
dc.language.iso | eng | |
dc.publisher | Impact Journals | |
dc.relation.ispartofpagefrom | 5755 | |
dc.relation.ispartofpageto | 5767 | |
dc.relation.ispartofissue | 56 | |
dc.relation.ispartofjournal | Oncotarget | |
dc.relation.ispartofvolume | 10 | |
dc.subject.fieldofresearch | Oncology and carcinogenesis | |
dc.subject.fieldofresearch | Cancer cell biology | |
dc.subject.fieldofresearchcode | 3211 | |
dc.subject.fieldofresearchcode | 321101 | |
dc.title | PTEN deletion drives acute myeloid leukaemia resistance to MEK inhibitors | |
dc.type | Journal article | |
dc.type.description | C1 - Articles | |
dcterms.bibliographicCitation | Smith, AM; Zhang, CRC; Cristino, A; Grady, JP; Fink, JL; Moore, AS, PTEN deletion drives acute myeloid leukaemia resistance to MEK inhibitors, Oncotarget, 2019, 10 (56), pp. 5755-5767 | |
dcterms.license | http://creativecommons.org/licenses/by/3.0/ | |
dc.date.updated | 2020-02-17T01:18:20Z | |
dc.description.version | Version of Record (VoR) | |
gro.rights.copyright | © 2019 Smith et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | |
gro.hasfulltext | Full Text | |
gro.griffith.author | Cristino, Alex | |