Vis enkel innførsel

dc.contributor.authorAndresen, Vibekeen_US
dc.contributor.authorErikstein, Bjarte Skoeen_US
dc.contributor.authorMukherjee, Herschelen_US
dc.contributor.authorSulen, Andreen_US
dc.contributor.authorPopa, Mihaela Luciaen_US
dc.contributor.authorSørnes, Steinaren_US
dc.contributor.authorReikvam, Håkonen_US
dc.contributor.authorChan, Kok-Pingen_US
dc.contributor.authorHovland, Randien_US
dc.contributor.authorMcCormack, Emmeten_US
dc.contributor.authorBruserud, Øysteinen_US
dc.contributor.authorMyers, Andrew G.en_US
dc.contributor.authorGjertsen, Bjørn Toreen_US
dc.PublishedAndresen 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:e2497eng
dc.description.abstractMutated 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.publisherNature Publishing Groupeng
dc.rightsAttribution CC BYeng
dc.titleAnti-proliferative activity of the NPM1 interacting natural product avrainvillamide in acute myeloid leukemiaen_US
dc.typePeer reviewed
dc.typeJournal article
dc.rights.holderCopyright 2016 The Author(s)
dc.source.journalCell Death & Disease

Tilhørende fil(er)


Denne innførselen finnes i følgende samling(er)

Vis enkel innførsel

Attribution CC BY
Med mindre annet er angitt, så er denne innførselen lisensiert som Attribution CC BY