Vis enkel innførsel

dc.contributor.authorNepstad, Inaen_US
dc.contributor.authorHatfield, Kimberley Joanneen_US
dc.contributor.authorTvedt, Tor Henrik Andersonen_US
dc.contributor.authorReikvam, Håkonen_US
dc.contributor.authorBruserud, Øysteinen_US
dc.PublishedNepstad I, Hatfield KJ, Tvedt THA, Reikvam H, Bruserud Ø. Clonal heterogeneity reflected by pi3k-akt-mtor signaling in human acute myeloid leukemia cells and its association with adverse prognosis. Cancers. 2018;10:332eng
dc.description.abstractClonal heterogeneity detected by karyotyping is a biomarker associated with adverse prognosis in acute myeloid leukemia (AML). Constitutive activation of the phosphatidylinositol-3-kinase-Akt-mechanistic target of rapamycin (PI3K-Akt-mTOR) pathway is present in AML cells, and this pathway integrates signaling from several upstream receptors/mediators. We suggest that this pathway reflects biologically important clonal heterogeneity. We investigated constitutive PI3K-Akt-mTOR pathway activation in primary human AML cells derived from 114 patients, together with 18 pathway mediators. The cohort included patients with normal karyotype or single karyotype abnormalities and with an expected heterogeneity of molecular genetic abnormalities. Clonal heterogeneity reflected as pathway mediator heterogeneity was detected for 49 patients. Global gene expression profiles of AML cell populations with and without clonal heterogeneity differed with regard to expression of ectopic olfactory receptors (a subset of G-protein coupled receptors) and proteins involved in G-protein coupled receptor signaling. Finally, the presence of clonal heterogeneity was associated with adverse prognosis for patients receiving intensive antileukemic treatment. The clonal heterogeneity as reflected in the activation status of selected mediators in the PI3K-Akt-mTOR pathway was associated with a different gene expression profile and had an independent prognostic impact. Biological heterogeneity reflected in the intracellular signaling status should be further investigated as a prognostic biomarker in human AML.en_US
dc.rightsAttribution CC BYeng
dc.titleClonal heterogeneity reflected by pi3k-akt-mtor signaling in human acute myeloid leukemia cells and its association with adverse prognosisen_US
dc.typePeer reviewed
dc.typeJournal article
dc.rights.holderCopyright The Author(s) 2018

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