dc.contributor.author | Selheim, Frode | |
dc.contributor.author | Aasebø, Elise | |
dc.contributor.author | Reikvam, Håkon | |
dc.contributor.author | Bruserud, Øystein | |
dc.contributor.author | Valladares, Maria del Carmen Hernandez | |
dc.date.accessioned | 2024-12-11T07:27:41Z | |
dc.date.available | 2024-12-11T07:27:41Z | |
dc.date.created | 2024-06-07T11:28:38Z | |
dc.date.issued | 2024-05-07 | |
dc.identifier.issn | 1661-6596 | |
dc.identifier.uri | https://hdl.handle.net/11250/3169158 | |
dc.description.abstract | Even 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.iso | eng | en_US |
dc.publisher | MDPI | en_US |
dc.rights | Navngivelse 4.0 Internasjonal | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/deed.no | * |
dc.title | Monocytic Differentiation of Human Acute Myeloid Leukemia Cells: A Proteomic and Phosphoproteomic Comparison of FAB-M4/M5 Patients with and without Nucleophosmin 1 Mutations | en_US |
dc.type | Journal article | en_US |
dc.type | Peer reviewed | en_US |
dc.description.version | publishedVersion | en_US |
dc.rights.holder | Copyright 2024 the authors | en_US |
dc.source.articlenumber | 5080 | en_US |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |
dc.identifier.doi | 10.3390/ijms25105080 | |
dc.identifier.cristin | 2274393 | |
dc.source.journal | International Journal of Molecular Sciences | en_US |
dc.identifier.citation | International Journal of Molecular Sciences. 2024, 25 (10), 5080. | en_US |
dc.source.volume | 25 | en_US |
dc.source.issue | 10 | en_US |