dc.contributor.author | Andresen, Vibeke | en_US |
dc.contributor.author | Erikstein, Bjarte Skoe | en_US |
dc.contributor.author | Mukherjee, Herschel | en_US |
dc.contributor.author | Sulen, Andre | en_US |
dc.contributor.author | Popa, Mihaela Lucia | en_US |
dc.contributor.author | Sørnes, Steinar | en_US |
dc.contributor.author | Reikvam, Håkon | en_US |
dc.contributor.author | Chan, Kok-Ping | en_US |
dc.contributor.author | Hovland, Randi | en_US |
dc.contributor.author | McCormack, Emmet | en_US |
dc.contributor.author | Bruserud, Øystein | en_US |
dc.contributor.author | Myers, Andrew G. | en_US |
dc.contributor.author | Gjertsen, Bjørn Tore | en_US |
dc.date.accessioned | 2017-08-04T12:26:57Z | |
dc.date.available | 2017-08-04T12:26:57Z | |
dc.date.issued | 2016-12-01 | |
dc.Published | Andresen V, Erikstein BS, Mukherjee H, Sulen A, Popa ML, Sørnes S, Reikvam H, Chan K, Hovland R, McCormack E, Bruserud Ø, Myers AG, Gjertsen BT. Anti-proliferative activity of the NPM1 interacting natural product avrainvillamide in acute myeloid leukemia. Cell Death & Disease. 2016;7:e2497 | eng |
dc.identifier.issn | 2041-4889 | |
dc.identifier.uri | https://hdl.handle.net/1956/16219 | |
dc.description.abstract | Mutated nucleophosmin 1 (NPM1) acts as a proto-oncogene and is present in ~30% of patients with acute myeloid leukemia (AML). Here we examined the in vitro and in vivo anti-leukemic activity of the NPM1 and chromosome region maintenance 1 homolog (CRM1) interacting natural product avrainvillamide (AVA) and a fully syntetic AVA analog. The NPM1-mutated cell line OCI-AML3 and normal karyotype primary AML cells with NPM1 mutations were significantly more sensitive towards AVA than cells expressing wild-type (wt) NPM1. Furthermore, the presence of wt p53 sensitized cells toward AVA. Cells exhibiting fms-like tyrosine kinase 3 (FLT3) internal tandem duplication mutations also displayed a trend toward increased sensitivity to AVA. AVA treatment induced nuclear retention of the NPM1 mutant protein (NPMc+) in OCI-AML3 cells and primary AML cells, caused proteasomal degradation of NPMc+ and the nuclear export factor CRM1 and downregulated wt FLT3 protein. In addition, both AVA and its analog induced differentiation of OCI-AML3 cells together with an increased phagocytotic activity and oxidative burst potential. Finally, the AVA analog displayed anti-proliferative activity against subcutaneous xenografted HCT-116 and OCI-AML3 cells in mice. Our results demonstrate that AVA displays enhanced potency against defined subsets of AML cells, suggesting that therapeutic intervention employing AVA or related compounds may be feasible. | en_US |
dc.language.iso | eng | eng |
dc.publisher | Nature Publishing Group | eng |
dc.rights | Attribution CC BY | eng |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0 | eng |
dc.title | Anti-proliferative activity of the NPM1 interacting natural product avrainvillamide in acute myeloid leukemia | en_US |
dc.type | Peer reviewed | |
dc.type | Journal article | |
dc.date.updated | 2017-05-10T07:50:56Z | |
dc.description.version | publishedVersion | en_US |
dc.rights.holder | Copyright 2016 The Author(s) | |
dc.identifier.doi | https://doi.org/10.1038/cddis.2016.392 | |
dc.identifier.cristin | 1427469 | |
dc.source.journal | Cell Death & Disease | |