{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T03:40:03Z","timestamp":1791258003574,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T00:00:00Z","timestamp":1648684800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T00:00:00Z","timestamp":1648684800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81800154"],"award-info":[{"award-number":["81800154"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Acute myeloid leukaemia (AML) is a highly heterogeneous haematologic malignancy with poor prognosis. We previously showed synergistic antileukaemic interaction between exportin 1 (XPO1) inhibitor KPT\u2010330 (Selinexor) and Bcl\u20102 inhibitor venetoclax (ABT\u2010199) in preclinical models of AML, which was partially meditated by Mcl\u20101, although the full mechanism of action remains unknown. In this study, using real\u2010time RT\u2010PCR and Western blot analysis, we show that inhibition of XPO1 via KPT\u2010330 or KPT\u20108602 (Eltanexor) decreases the mRNA and protein levels of c\u2010Myc, CHK1, WEE1, RAD51 and RRM2. KPT\u2010330 and KPT\u20108602 induce DNA damage, as determined by alkaline comet assay. In addition, we demonstrate that venetoclax enhances KPT\u2010330\u2010 and KPT\u20108602\u2010induced DNA damage, likely through inhibition of DNA damage repair. This study provides new insight into the molecular mechanism underlying the synergistic antileukaemic activity between venetoclax and XPO1 inhibitors against AML. Our data support the clinical evaluation of this promising combination therapy for the treatment of AML.<\/jats:p>","DOI":"10.1111\/jcmm.17274","type":"journal-article","created":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T03:49:28Z","timestamp":1648698568000},"page":"2646-2657","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Venetoclax enhances DNA damage induced by XPO1 inhibitors: A novel mechanism underlying the synergistic antileukaemic effect in acute myeloid leukaemia"],"prefix":"10.1111","volume":"26","author":[{"given":"Hanxi","family":"Yu","sequence":"first","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine Key Laboratory for Molecular Enzymology and Engineering the Ministry of Education School of Life Sciences Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangshuang","family":"Wu","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine Key Laboratory for Molecular Enzymology and Engineering the Ministry of Education School of Life Sciences Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Liu","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine Key Laboratory for Molecular Enzymology and Engineering the Ministry of Education School of Life Sciences Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Li","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine Key Laboratory for Molecular Enzymology and Engineering the Ministry of Education School of Life Sciences Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqing","family":"Gai","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine Key Laboratory for Molecular Enzymology and Engineering the Ministry of Education School of Life Sciences Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology the First Hospital of Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology the First Hospital of Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly","family":"Edwards","sequence":"additional","affiliation":[{"name":"Department of Oncology and Molecular Therapeutics Program Barbara Ann Karmanos Cancer Institute Wayne State University School of Medicine  Detroit Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8748-716X","authenticated-orcid":false,"given":"Yubin","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Oncology and Molecular Therapeutics Program Barbara Ann Karmanos Cancer Institute Wayne State University School of Medicine  Detroit Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1407-5778","authenticated-orcid":false,"given":"Guan","family":"Wang","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine Key Laboratory for Molecular Enzymology and Engineering the Ministry of Education School of Life Sciences Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,3,31]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.14823"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-020-00361-x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beha.2019.05.008"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2010.09.008"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-04-423160"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.24146"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.23354"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2012.074781"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2012.219"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-019-01188-9"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/14656566.2019.1707184"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-08-797886"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-1580"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2016.136"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2016.145"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.13886"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2006.07.014"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12094-012-0926-8"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2018.1464158"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-014-2495-8"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-2885"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-11-750174"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.25637"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-017-2226-0"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes8020057"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.15281"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11523-019-00638-4"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.201343"},{"key":"e_1_2_9_30_1","first-page":"13","article-title":"Detection of mycoplasma contaminations","volume":"290","author":"Uphoff CC","year":"2005","journal-title":"Methods Mol Biol"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-021-00502-7"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2015.07.029"},{"key":"e_1_2_9_34_1","first-page":"611","article-title":"RRM1, RRM2 and ERCC2 Gene Polymorphisms in Coronary Artery Disease","volume":"30","author":"Altinkilic EM","year":"2016","journal-title":"In Vivo (Athens, Greece)"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-10-0523"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008924"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1206641"},{"key":"e_1_2_9_38_1","first-page":"1262","article-title":"The HDAC and PI3K dual inhibitor CUDC\u2010907 synergistically enhances the antileukemic activity of venetoclax in preclinical models of acute myeloid leukemia","volume":"106","author":"Li X","year":"2021","journal-title":"Haematologica"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molonc.2014.09.008"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgx016"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.140350"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2467"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e12-01-0045"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01876-08"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3048"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2019000359"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.17274","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jcmm.17274","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.17274","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T11:50:26Z","timestamp":1771329026000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.17274"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,31]]},"references-count":45,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2022,5]]}},"alternative-id":["10.1111\/jcmm.17274"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.17274","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"value":"1582-1838","type":"print"},{"value":"1582-4934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,31]]},"assertion":[{"value":"2021-10-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}