{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:15:36Z","timestamp":1790255736680,"version":"4.1.0"},"reference-count":36,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:00:00Z","timestamp":1767916800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hematology Reports"],"abstract":"<jats:p>Background\/Objectives: Aurora kinases (AURKs) are key regulators of mitosis, and their dysregulation contributes to plasma cell disorders, including multiple myeloma (MM) and plasma cell leukemia (PCL). Methods: The expression and prognostic relevance of AURK family members were examined, and the therapeutic potential of AURKA inhibition was evaluated. Results: Gene expression analysis demonstrated significant upregulation of AURKA in PCL. Treatment of MM cells with the selective AURKA inhibitor LY3295668 induced dose-dependent cytotoxicity, caspase-3\/7 activation, and cellular senescence. Similarly, selinexor, a selective exportin-1 inhibitor, elicited dose-dependent cytotoxicity and apoptosis. Combined treatment with LY3295668 and selinexor significantly improved apoptosis compared with either agent alone, and AURKA knockdown further sensitized MM cells to selinexor, thereby increasing apoptosis. In bortezomib-resistant MM cells and primary PCL samples, the combination therapy induced cytotoxicity and caspase-3\/7 activation. Conclusions: These findings underscore AURKA expression as a prognostic marker in plasma cell disorders and support the therapeutic potential of combining AURKA inhibition with selinexor for bortezomib-resistant MM and PCL. To explore biomarker-driven strategies for optimizing therapeutic outcomes, future studies are warranted.<\/jats:p>","DOI":"10.3390\/hematolrep18010010","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T10:35:52Z","timestamp":1767954952000},"page":"10","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Therapeutic Potential of Exportin 1 and Aurora Kinase A Inhibition in Multiple Myeloma Cells"],"prefix":"10.3390","volume":"18","author":[{"given":"Seiichi","family":"Okabe","sequence":"first","affiliation":[{"name":"Department of Hematology, Tokyo Medical University, Tokyo 1600023, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1114-8188","authenticated-orcid":false,"given":"Yuko","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Hematology, Tokyo Medical University, Tokyo 1600023, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunsuke","family":"Otsuki","sequence":"additional","affiliation":[{"name":"Department of Hematology, Tokyo Medical University, Tokyo 1600023, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuru","family":"Moriyama","sequence":"additional","affiliation":[{"name":"Department of Hematology, Tokyo Medical University, Tokyo 1600023, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiichiro","family":"Yoshizawa","sequence":"additional","affiliation":[{"name":"Department of Hematology, Tokyo Medical University, Tokyo 1600023, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8608-4393","authenticated-orcid":false,"given":"Akihiko","family":"Gotoh","sequence":"additional","affiliation":[{"name":"Department of Hematology, Tokyo Medical University, Tokyo 1600023, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daigo","family":"Akahane","sequence":"additional","affiliation":[{"name":"Department of Hematology, Tokyo Medical University, Tokyo 1600023, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/s41572-024-00529-7","article-title":"Multiple myeloma","volume":"10","author":"Malard","year":"2024","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2599","DOI":"10.1182\/blood-2016-09-692954","article-title":"MGUS to myeloma: A mysterious gammopathy of underexplored significance","volume":"128","author":"Dhodapkar","year":"2016","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.1158\/0008-5472.CAN-17-3115","article-title":"From MGUS to multiple myeloma, a paradigm for clonal evolution of premalignant cells","volume":"78","author":"Spaan","year":"2018","journal-title":"Cancer Res."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Rojas, E.A., and Guti\u00e9rrez, N.C. (2022). Genomics of plasma cell leukemia. Cancers, 14.","DOI":"10.3390\/cancers14061594"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1038\/s41408-021-00587-0","article-title":"Primary plasma cell leukemia: Consensus definition by the International Myeloma Working Group according to peripheral blood plasma cell percentage","volume":"11","author":"Kyle","year":"2021","journal-title":"Blood Cancer J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"115875","DOI":"10.1016\/j.ejmech.2023.115875","article-title":"Advances in research on potential inhibitors of multiple myeloma","volume":"262","author":"Tang","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1007\/s12032-007-0007-y","article-title":"Clinical stage-depending decrease of NK cell activity in multiple myeloma patients","volume":"24","author":"Jurisic","year":"2007","journal-title":"Med. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1385\/MO:19:3:133","article-title":"Correlation of sera TNF-alpha with percentage of bone marrow plasma cells, LDH, beta2-microglobulin, and clinical stage in multiple myeloma","volume":"19","year":"2002","journal-title":"Med. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1002\/jha2.709","article-title":"Selinexor: Targeting a novel pathway in multiple myeloma","volume":"4","author":"Mo","year":"2023","journal-title":"eJHaem"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4142","DOI":"10.1200\/JCO.2015.65.3949","article-title":"First-in-class, first-in-human phase i study of selinexor, a selective inhibitor of nuclear export, in patients with advanced solid tumors","volume":"34","author":"Gabrail","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1080\/13543776.2021.1890027","article-title":"Aurora kinase inhibitors: A patent review (2014\u20132020)","volume":"31","author":"Jing","year":"2021","journal-title":"Expert. Opin. Ther. Pat."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.gde.2003.11.006","article-title":"Aurora kinases link chromosome segregation and cell division to cancer susceptibility","volume":"14","author":"Meraldi","year":"2004","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.yexcr.2004.08.016","article-title":"Aurora kinases in spindle assembly and chromosome segregation","volume":"301","author":"Ducat","year":"2004","journal-title":"Exp. Cell Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1038\/s12276-021-00635-6","article-title":"Aurora kinase A, a synthetic lethal target for precision cancer medicine","volume":"53","author":"Mou","year":"2021","journal-title":"Exp. Mol. Med."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Bavetsias, V., and Linardopoulos, S. (2015). Aurora kinase inhibitors: Current status and outlook. Front. Oncol., 5.","DOI":"10.3389\/fonc.2015.00278"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1007\/s10637-020-01049-3","article-title":"Aurora kinase A inhibitor, LY3295668 erbumine: A phase 1 monotherapy safety study in patients with locally advanced or metastatic solid tumors","volume":"39","author":"Chu","year":"2021","journal-title":"Investig. New Drugs"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1038\/leu.2010.137","article-title":"Bortezomib-resistant myeloma cell lines: A role for mutated PSMB5 in preventing the accumulation of unfolded proteins and fatal ER stress","volume":"24","author":"Ri","year":"2010","journal-title":"Leukemia"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1002\/gcc.20668","article-title":"A SNP microarray and FISH-based procedure to detect allelic imbalances in multiple myeloma: An integrated genomics approach reveals a wide gene dosage effect","volume":"48","author":"Agnelli","year":"2009","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1158\/0008-5472.CAN-09-1947","article-title":"Drug combination studies and their synergy quantification using the Chou-Talalay method","volume":"70","author":"Chou","year":"2010","journal-title":"Cancer Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.canlet.2004.05.011","article-title":"Modulation of TNF-alpha activity in tumor PC cells using anti-CD45 and anti-CD95 monoclonal antibodies","volume":"214","author":"Bogdanovic","year":"2004","journal-title":"Cancer Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"541","DOI":"10.2298\/VSP240422050J","article-title":"The importance of determining lactate dehydrogenase in laboratory and experimental work in oncology","volume":"81","author":"Balint","year":"2024","journal-title":"Vojnosanit. Pregl."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/1756-8722-7-37","article-title":"Combination of the ABL kinase inhibitor imatinib with the Janus kinase 2 inhibitor TG101348 for targeting residual BCR-ABL-positive cells","volume":"7","author":"Okabe","year":"2014","journal-title":"J. Hematol. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e062504","DOI":"10.1136\/bmjopen-2022-062504","article-title":"MUK twelve protocol: A phase II randomized, controlled, open, parallel group, multicenter trial of selinexor, cyclophosphamide and prednisolone (SCP) versus cyclophosphamide and prednisolone (CP) in patients with relapsed or refractory multiple myeloma","volume":"12","author":"Kendall","year":"2022","journal-title":"BMJ Open"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1038\/s41375-021-01483-z","article-title":"Selective inhibition of nuclear export: A promising approach in the shifting treatment paradigms for hematological neoplasms","volume":"36","author":"Balasubramanian","year":"2022","journal-title":"Leukemia"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2207","DOI":"10.1158\/1535-7163.MCT-18-0529","article-title":"Aurora A-Selective Inhibitor LY3295668 Leads to Dominant Mitotic Arrest, Apoptosis in Cancer Cells, and Shows Potent Preclinical Antitumor Efficacy","volume":"18","author":"Du","year":"2019","journal-title":"Mol. Cancer Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1158\/1078-0432.CCR-24-2290","article-title":"Phase I\/II study of the Aurora kinase A inhibitor alisertib and pembrolizumab in refractory, Rb-deficient head and neck squamous cell carcinomas","volume":"31","author":"Johnson","year":"2025","journal-title":"Clin. Cancer Res."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Davis, S.L., Messersmith, W.A., Purcell, W.T., Lam, E.T., Corr, B.R., Leal, A.D., Lieu, C.H., O\u2019bryant, C.L., Smoots, S.G., and Dus, E.D. (2024). A phase Ib expansion cohort evaluating aurora A kinase inhibitor alisertib and dual TORC1\/2 inhibitor sapanisertib in patients with advanced solid tumors. Cancers, 16.","DOI":"10.3390\/cancers16081456"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e35751","DOI":"10.1002\/cncr.35751","article-title":"A phase 1 dose-esc alation study of LY3295668 erbumine as monotherapy and in combination with topotecan and cyclophosphamide in children with relapsed\/refractory neuroblastoma","volume":"131","author":"DuBois","year":"2025","journal-title":"Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1001\/jamaoncol.2022.7949","article-title":"Evaluation of alisertib alone or combined with fulvestrant in patients with endocrine-resistant advanced breast cancer: The Phase 2 TBCRC041 randomized clinical trial","volume":"9","author":"Haddad","year":"2023","journal-title":"JAMA Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1158\/2767-9764.CRC-23-0482","article-title":"Synergy of EGFR and AURKA inhibitors in KRAS-mutated non-small cell lung cancers","volume":"4","author":"Bagnyukova","year":"2024","journal-title":"Cancer Res. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e161929","DOI":"10.1172\/JCI161929","article-title":"Aurora A kinase inhibition compromises its antitumor efficacy by elevating PD-L1 expression","volume":"133","author":"Wang","year":"2023","journal-title":"J. Clin. Investig."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1093\/neuonc\/noac151","article-title":"Phase II study of alisertib as a single agent for treating recurrent or progressive atypical teratoid\/rhabdoid tumor","volume":"25","author":"Upadhyaya","year":"2023","journal-title":"Neuro Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1111\/bjh.13765","article-title":"A phase Ib study of the combination of the aurora kinase inhibitor alisertib (MLN8237) and bortezomib in relapsed multiple myeloma","volume":"174","author":"Rosenthal","year":"2016","journal-title":"Br. J. Haematol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2875","DOI":"10.1038\/s41375-020-0958-y","article-title":"Targeting nuclear import and export in hematological malignancies","volume":"34","author":"Nachmias","year":"2020","journal-title":"Leukemia"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Polverino, F., Mastrangelo, A., and Guarguaglini, G. (2024). Contribution of AurkA\/TPX2 Overexpression to chromosomal imbalances and cancer. Cells, 13.","DOI":"10.3390\/cells13161397"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1007\/s12032-024-02394-6","article-title":"Combination of an aurora kinase inhibitor and the ABL tyrosine kinase inhibitor asciminib against ABL inhibitor-resistant CML cells","volume":"41","author":"Okabe","year":"2024","journal-title":"Med. Oncol."}],"container-title":["Hematology Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2038-8330\/18\/1\/10\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T10:56:19Z","timestamp":1767956179000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2038-8330\/18\/1\/10"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,9]]},"references-count":36,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["hematolrep18010010"],"URL":"https:\/\/doi.org\/10.3390\/hematolrep18010010","relation":{},"ISSN":["2038-8330"],"issn-type":[{"value":"2038-8330","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,9]]}}}