{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T04:22:32Z","timestamp":1785558152447,"version":"3.56.0"},"reference-count":133,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T00:00:00Z","timestamp":1737676800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Exportin 1 is responsible for the export of hundreds of proteins, several RNA species and ribosomal components from the nucleus to the cytoplasm. Several transported proteins are important for regulation of cell proliferation and survival both in normal and malignant cells. We review the biological importance and the possibility of therapeutic targeting of Exportin 1 in acute myeloid leukemia (AML). Exportin 1 levels can be increased in human primary AML cells, and even exportin inhibition as monotherapy seems to have an antileukemic effect. The results from Phase I\/II studies also suggest that exportin inhibition can be combined with conventional chemotherapy, including intensive induction and consolidation therapy possibly followed by allogeneic stem cell transplantation as well as AML-stabilizing therapy in elderly\/unfit patients with hypomethylating agents. However, the risk of severe toxicity needs to be further evaluated; hematological toxicity is common together with constitutional side effects, electrolyte disturbances, and gastrointestinal toxicity. A recent randomized study of intensive chemotherapy with and without the Exportin inhibitor selinexor in elderly patients showed reduced survival in the selinexor arm; this was due to a high frequency of relapse and severe infections during neutropenia. Experimental studies suggest that Exportin 1 inhibition can be combined with other forms of targeted therapy. Thus, Exportin 1 inhibition should still be regarded as a promising strategy for AML treatment, but future studies should focus on the risk of toxicity when combined with conventional chemotherapy, especially in elderly\/unfit patients, combinations with targeted therapies, identification of patient subsets (AML is a heterogeneous disease) with high susceptibility, and the possible use of less toxic next-generation Exportin 1 inhibitors.<\/jats:p>","DOI":"10.3390\/biom15020175","type":"journal-article","created":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T11:50:47Z","timestamp":1737719447000},"page":"175","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["XPO1\/Exportin-1 in Acute Myelogenous Leukemia; Biology and Therapeutic Targeting"],"prefix":"10.3390","volume":"15","author":[{"given":"\u00d8ystein","family":"Bruserud","sequence":"first","affiliation":[{"name":"Acute Leukemia Research Group, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway"},{"name":"Section for Hematology, Department of Medicine, Haukeland University Hospital, 5007 Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frode","family":"Selheim","sequence":"additional","affiliation":[{"name":"Proteomics Unit of University of Bergen (PROBE), University of Bergen, Jonas Lies Vei 91, 5009 Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Hernandez-Valladares","sequence":"additional","affiliation":[{"name":"Acute Leukemia Research Group, Department of Clinical Science, University of Bergen, 5021 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"}]},{"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, 5021 Bergen, Norway"},{"name":"Section for Hematology, Department of Medicine, Haukeland University Hospital, 5007 Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,24]]},"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 genomic data","volume":"140","author":"Arber","year":"2022","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1182\/blood-2016-03-643544","article-title":"The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia","volume":"127","author":"Arber","year":"2016","journal-title":"Blood"},{"key":"ref_3","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_4","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/1868-7083-5-13","article-title":"The combination of valproic acid, all-trans retinoic acid and low-dose cytarabine as disease-stabilizing treatment in acute myeloid leukemia","volume":"5","author":"Fredly","year":"2013","journal-title":"Clin. 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