{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T22:09:13Z","timestamp":1793830153128,"version":"4.6.1"},"reference-count":146,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T00:00:00Z","timestamp":1715040000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008730","name":"Norwegian Cancer Society","doi-asserted-by":"publisher","award":["100933"],"award-info":[{"award-number":["100933"]}],"id":[{"id":"10.13039\/100008730","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008730","name":"Norwegian Cancer Society","doi-asserted-by":"publisher","award":["295910"],"award-info":[{"award-number":["295910"]}],"id":[{"id":"10.13039\/100008730","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Research Council of Norway INFRASTRUKTUR-program","award":["100933"],"award-info":[{"award-number":["100933"]}]},{"name":"Research Council of Norway INFRASTRUKTUR-program","award":["295910"],"award-info":[{"award-number":["295910"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms25105080","type":"journal-article","created":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T09:03:38Z","timestamp":1715072618000},"page":"5080","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"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"],"prefix":"10.3390","volume":"25","author":[{"given":"Frode","family":"Selheim","sequence":"first","affiliation":[{"name":"Proteomics Unit of University of Bergen (PROBE), University of Bergen, Jonas Lies vei 91, 5009 Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6939-8059","authenticated-orcid":false,"given":"Elise","family":"Aaseb\u00f8","sequence":"additional","affiliation":[{"name":"Acute Leukemia Research Group, Department of Clinical Science, University of Bergen, Jonas Lies vei 91, 5009 Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5439-8411","authenticated-orcid":false,"given":"H\u00e5kon","family":"Reikvam","sequence":"additional","affiliation":[{"name":"Acute Leukemia Research Group, Department of Clinical Science, University of Bergen, Jonas Lies vei 91, 5009 Bergen, Norway"},{"name":"Section for Hematology, Department of Medicine, Haukeland University Hospital, 5009 Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d8ystein","family":"Bruserud","sequence":"additional","affiliation":[{"name":"Acute Leukemia Research Group, Department of Clinical Science, University of Bergen, Jonas Lies vei 91, 5009 Bergen, Norway"},{"name":"Section for Hematology, Department of Medicine, Haukeland University Hospital, 5009 Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9347-7841","authenticated-orcid":false,"given":"Maria","family":"Hernandez-Valladares","sequence":"additional","affiliation":[{"name":"Proteomics Unit of University of Bergen (PROBE), University of Bergen, Jonas Lies vei 91, 5009 Bergen, Norway"},{"name":"Department of Physical Chemistry, University of Granada, Avenida de la Fuente Nueva S\/N, 18071 Granada, Spain"},{"name":"Instituto de Investigaci\u00f3n Biosanitaria ibs.GRANADA, 18012 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1182\/blood.2022015850","article-title":"International Consensus Classification of Myeloid Neoplasms and Acute Leukemias: Integrating morphologic, clinical, and enomic data","volume":"140","author":"Arber","year":"2022","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1182\/blood.2022016867","article-title":"Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN","volume":"140","author":"Wei","year":"2022","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"101626","DOI":"10.1016\/j.jgo.2023.101626","article-title":"Treating acute myelogenous leukemia in patients aged 70 and above: Recommendations from the International Society of Geriatric Oncology (SIOG)","volume":"15","author":"Extermann","year":"2023","journal-title":"J. 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