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dc.contributor.authorSelheim, Frode
dc.contributor.authorAasebø, Elise
dc.contributor.authorReikvam, Håkon
dc.contributor.authorBruserud, Øystein
dc.contributor.authorValladares, Maria del Carmen Hernandez
dc.date.accessioned2024-12-11T07:27:41Z
dc.date.available2024-12-11T07:27:41Z
dc.date.created2024-06-07T11:28:38Z
dc.date.issued2024-05-07
dc.identifier.issn1661-6596
dc.identifier.urihttps://hdl.handle.net/11250/3169158
dc.description.abstractEven though morphological signs of differentiation have a minimal impact on survival after intensive cytotoxic therapy for acute myeloid leukemia (AML), monocytic AML cell differentiation (i.e., classified as French/American/British (FAB) subtypes M4/M5) is associated with a different responsiveness both to Bcl-2 inhibition (decreased responsiveness) and possibly also bromodomain inhibition (increased responsiveness). FAB-M4/M5 patients are heterogeneous with regard to genetic abnormalities, even though monocytic differentiation is common for patients with Nucleophosmin 1 (NPM1) insertions/mutations; to further study the heterogeneity of FAB-M4/M5 patients we did a proteomic and phosphoproteomic comparison of FAB-M4/M5 patients with (n = 13) and without (n = 12) NPM1 mutations. The proteomic profile of NPM1-mutated FAB-M4/M5 patients was characterized by increased levels of proteins involved in the regulation of endocytosis/vesicle trafficking/organellar communication. In contrast, AML cells without NPM1 mutations were characterized by increased levels of several proteins involved in the regulation of cytoplasmic translation, including a large number of ribosomal proteins. The phosphoproteomic differences between the two groups were less extensive but reflected similar differences. To conclude, even though FAB classification/monocytic differentiation are associated with differences in responsiveness to new targeted therapies (e.g., Bcl-2 inhibition), our results shows that FAB-M4/M5 patients are heterogeneous with regard to important biological characteristics of the leukemic cells.en_US
dc.language.isoengen_US
dc.publisherMDPIen_US
dc.rightsNavngivelse 4.0 Internasjonal*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/deed.no*
dc.titleMonocytic Differentiation of Human Acute Myeloid Leukemia Cells: A Proteomic and Phosphoproteomic Comparison of FAB-M4/M5 Patients with and without Nucleophosmin 1 Mutationsen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.description.versionpublishedVersionen_US
dc.rights.holderCopyright 2024 the authorsen_US
dc.source.articlenumber5080en_US
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode1
dc.identifier.doi10.3390/ijms25105080
dc.identifier.cristin2274393
dc.source.journalInternational Journal of Molecular Sciencesen_US
dc.identifier.citationInternational Journal of Molecular Sciences. 2024, 25 (10), 5080.en_US
dc.source.volume25en_US
dc.source.issue10en_US


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Navngivelse 4.0 Internasjonal
Except where otherwise noted, this item's license is described as Navngivelse 4.0 Internasjonal