{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T09:10:22Z","timestamp":1778836222669,"version":"3.51.4"},"reference-count":45,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T00:00:00Z","timestamp":1744675200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008865","name":"Xiamen University","doi-asserted-by":"publisher","award":["XMULAC20170065"],"award-info":[{"award-number":["XMULAC20170065"]}],"id":[{"id":"10.13039\/501100008865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81700161"],"award-info":[{"award-number":["81700161"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2020J011239"],"award-info":[{"award-number":["2020J011239"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2021J011348"],"award-info":[{"award-number":["2021J011348"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Translational Oncology"],"published-print":{"date-parts":[[2025,7]]},"DOI":"10.1016\/j.tranon.2025.102399","type":"journal-article","created":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T19:45:56Z","timestamp":1747165556000},"page":"102399","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"special_numbering":"C","title":["The synergy of TPL and selinexor in MLL-R acute myeloid leukemia via Rap1\/Raf\/MEK pathway-mediated MYC downregulation"],"prefix":"10.1016","volume":"57","author":[{"given":"Manman","family":"Deng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peicui","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lijuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuelong","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenling","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongpeng","family":"Duan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Zha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haijun","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guowei","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bing","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"issue":"5","key":"10.1016\/j.tranon.2025.102399_bib0001","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1038\/s41375-023-01877-1","article-title":"The KMT2A recombinome of acute leukemias in 2023","volume":"37","author":"Meyer","year":"2023","journal-title":"Leukemia"},{"issue":"5","key":"10.1016\/j.tranon.2025.102399_bib0002","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1080\/13543776.2022.2045947","article-title":"Menin-MLL protein-protein interaction inhibitors: a patent review (2014-2021)","volume":"32","author":"Bai","year":"2022","journal-title":"Expert Opin. Ther. Pat."},{"issue":"11","key":"10.1016\/j.tranon.2025.102399_bib0003","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.3390\/cells8111341","article-title":"MLL-rearranged acute leukemia with t(4;11)(q21;q23)-current treatment options. Is there a role for CAR-T cell therapy?","volume":"8","author":"Britten","year":"2019","journal-title":"Cells"},{"key":"10.1016\/j.tranon.2025.102399_bib0004","doi-asserted-by":"crossref","first-page":"2395","DOI":"10.1182\/blood-2003-02-0434","article-title":"AML with 11q23\/MLL abnormalities as defined by the WHO classification: incidence, partner chromosomes, FAB subtype, age distribution, and prognostic impact in an unselected series of 1897 cytogenetically analyzed AML cases","volume":"102","author":"Schoch","year":"2003","journal-title":"Blood"},{"issue":"1","key":"10.1016\/j.tranon.2025.102399_bib0005","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/s41408-021-00603-3","article-title":"Effective Menin inhibitor-based combinations against AML with MLL rearrangement or NPM1 mutation (NPM1c)","volume":"12","author":"Fiskus","year":"2022","journal-title":"Blood Cancer J."},{"issue":"6","key":"10.1016\/j.tranon.2025.102399_bib0006","doi-asserted-by":"crossref","DOI":"10.1016\/j.ccell.2019.11.001","article-title":"A Menin-MLL inhibitor induces specific chromatin changes and eradicates disease in models of MLL-rearranged leukemia","volume":"36","author":"Krivtsov","year":"2019","journal-title":"Cancer Cell"},{"issue":"9","key":"10.1016\/j.tranon.2025.102399_bib0007","doi-asserted-by":"crossref","first-page":"2482","DOI":"10.1038\/s41375-021-01309-y","article-title":"Therapeutic implications of menin inhibition in acute leukemias","volume":"35","author":"Issa","year":"2021","journal-title":"Leukemia"},{"issue":"1","key":"10.1016\/j.tranon.2025.102399_bib0008","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1186\/s13148-019-0723-0","article-title":"Co-inhibition of HDAC and MLL-menin interaction targets MLL-rearranged acute myeloid leukemia cells via disruption of DNA damage checkpoint and DNA repair","volume":"11","author":"Ye","year":"2019","journal-title":"Clin. Epigenetics"},{"issue":"3","key":"10.1016\/j.tranon.2025.102399_bib0009","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1038\/s41571-020-00442-4","article-title":"The nuclear export protein XPO1 - from biology to targeted therapy","volume":"18","author":"Azmi","year":"2021","journal-title":"Nat. Rev. Clin. Oncol."},{"issue":"1","key":"10.1016\/j.tranon.2025.102399_bib0010","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/leu.2013.115","article-title":"CRM1 inhibition induces tumor cell cytotoxicity and impairs osteoclastogenesis in multiple myeloma: molecular mechanisms and therapeutic implications","volume":"28","author":"Tai","year":"2014","journal-title":"Leukemia"},{"issue":"1","key":"10.1016\/j.tranon.2025.102399_bib0011","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1186\/s13045-020-00982-3","article-title":"XPO1 expression worsens the prognosis of unfavorable DLBCL that can be effectively targeted by selinexor in the absence of mutant p53","volume":"13","author":"Deng","year":"2020","journal-title":"J. Hematol. Oncol."},{"issue":"5","key":"10.1016\/j.tranon.2025.102399_bib0012","doi-asserted-by":"crossref","DOI":"10.3390\/jcm8050596","article-title":"XPO1 Expression is a poor-prognosis marker in pancreatic adenocarcinoma","volume":"8","author":"Birnbaum","year":"2019","journal-title":"J. Clin. Med."},{"issue":"22","key":"10.1016\/j.tranon.2025.102399_bib0013","doi-asserted-by":"crossref","first-page":"5938","DOI":"10.1182\/bloodadvances.2022007563","article-title":"Prolonged XPO1 inhibition is essential for optimal antileukemic activity in NPM1-mutated AML","volume":"6","author":"Pianigiani","year":"2022","journal-title":"Blood Adv"},{"issue":"3","key":"10.1016\/j.tranon.2025.102399_bib0014","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1158\/0008-5472.CAN-21-2964","article-title":"Inhibition of XPO1 sensitizes small cell lung cancer to first- and second-line chemotherapy","volume":"82","author":"Quintanal-Villalonga","year":"2022","journal-title":"Cancer Res."},{"issue":"1","key":"10.1016\/j.tranon.2025.102399_bib0015","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1053\/j.gastro.2021.03.022","article-title":"A. Sequential administration of XPO1 and ATR inhibitors enhances therapeutic response in TP53-mutated colorectal cancer","volume":"161","author":"Inoue","year":"2021","journal-title":"Gastroenterology"},{"issue":"10262","key":"10.1016\/j.tranon.2025.102399_bib0016","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1016\/S0140-6736(20)32292-3","article-title":"Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): a randomised, open-label, phase 3 trial","volume":"396","author":"Grosicki","year":"2020","journal-title":"Lancet"},{"issue":"22","key":"10.1016\/j.tranon.2025.102399_bib0017","doi-asserted-by":"crossref","first-page":"2479","DOI":"10.1200\/JCO.21.01829","article-title":"Selinexor in advanced, metastatic dedifferentiated liposarcoma: a multinational, randomized, double-blind, placebo-controlled trial","volume":"40","author":"Gounder","year":"2022","journal-title":"J. Clin. Oncol."},{"issue":"1","key":"10.1016\/j.tranon.2025.102399_bib0018","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s13045-017-0550-8","article-title":"A phase I study of selinexor in combination with high-dose cytarabine and mitoxantrone for remission induction in patients with acute myeloid leukemia","volume":"11","author":"Wang","year":"2018","journal-title":"J. Hematol. Oncol."},{"issue":"15","key":"10.1016\/j.tranon.2025.102399_bib0019","doi-asserted-by":"crossref","first-page":"7199","DOI":"10.7150\/thno.57745","article-title":"Triptolide: pharmacological spectrum, biosynthesis, chemical synthesis and derivatives","volume":"11","author":"Gao","year":"2021","journal-title":"Theranostics"},{"issue":"5","key":"10.1016\/j.tranon.2025.102399_bib0020","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.tips.2019.03.002","article-title":"Triptolide and its derivatives as cancer therapies","volume":"40","author":"Noel","year":"2019","journal-title":"Trends Pharmacol. Sci."},{"issue":"1","key":"10.1016\/j.tranon.2025.102399_bib0021","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s40164-022-00276-z","article-title":"Therapeutic synergy of Triptolide and MDM2 inhibitor against acute myeloid leukemia through modulation of p53-dependent and -independent pathways","volume":"11","author":"Chen","year":"2022","journal-title":"Exp. Hematol. Oncol."},{"issue":"9","key":"10.1016\/j.tranon.2025.102399_bib0022","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1002\/mc.23238","article-title":"Low-dose triptolide enhances antitumor effect of JQ1 on acute myeloid leukemia through inhibiting RNA polymerase II in vitro and in vivo","volume":"59","author":"Shi","year":"2020","journal-title":"Mol. Carcinog."},{"issue":"7","key":"10.1016\/j.tranon.2025.102399_bib0023","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/s41419-020-02762-w","article-title":"Combining triptolide with ABT-199 is effective against acute myeloid leukemia through reciprocal regulation of bcl-2 family proteins and activation of the intrinsic apoptotic pathway","volume":"11","author":"Shi","year":"2020","journal-title":"Cell. Death. Dis."},{"issue":"1","key":"10.1016\/j.tranon.2025.102399_bib0024","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/s13046-021-01886-x","article-title":"Selinexor versus doxorubicin in dedifferentiated liposarcoma PDXs: evidence of greater activity and apoptotic response dependent on p53 nuclear accumulation and survivin down-regulation","volume":"40","author":"Zuco","year":"2021","journal-title":"J. Exp. Clin. Cancer Res."},{"issue":"8","key":"10.1016\/j.tranon.2025.102399_bib0025","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1038\/sj.cdd.4401962","article-title":"The p53-Bcl-2 connection","volume":"13","author":"Hemann","year":"2006","journal-title":"Cell Death Differ."},{"key":"10.1016\/j.tranon.2025.102399_bib0026","doi-asserted-by":"crossref","first-page":"4","DOI":"10.3389\/fped.2017.00004","article-title":"MLL-rearranged leukemias-an update on science and clinical approaches","volume":"5","author":"Winters","year":"2017","journal-title":"Front Pediatr"},{"key":"10.1016\/j.tranon.2025.102399_bib0027","doi-asserted-by":"crossref","first-page":"3254","DOI":"10.1200\/JCO.2002.09.088","article-title":"Prognostic significance of partial tandem duplications of the MLL gene in adult patients 16 to 60 years old with acute myeloid leukemia and normal cytogenetics: a study of the Acute Myeloid Leukemia Study Group Ulm","volume":"20","author":"Dohner","year":"2002","journal-title":"J. Clin. Oncol."},{"issue":"7","key":"10.1016\/j.tranon.2025.102399_bib0028","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1056\/NEJMoa2012971","article-title":"Azacitidine and venetoclax in previously untreated acute myeloid leukemia","volume":"383","author":"DiNardo","year":"2020","journal-title":"N. Engl. J. Med."},{"issue":"1","key":"10.1016\/j.tranon.2025.102399_bib0029","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/s41392-020-0113-2","article-title":"Advances in targeted therapy for malignant lymphoma","volume":"5","author":"Wang","year":"2020","journal-title":"Signal. Transduct. Target. Ther"},{"issue":"18","key":"10.1016\/j.tranon.2025.102399_bib0030","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1056\/NEJMoa1902688","article-title":"Gilteritinib or chemotherapy for relapsed or refractory FLT3-mutated AML","volume":"381","author":"Perl","year":"2019","journal-title":"N. Engl. J. Med."},{"issue":"Supplement 1","key":"10.1016\/j.tranon.2025.102399_bib0031","doi-asserted-by":"crossref","first-page":"8811","DOI":"10.1182\/blood-2022-168151","article-title":"Novel combination of clinical menin inhibitor Ziftomenib and the nuclear export inhibitor Selinexor synergistically inhibit MLL-r AML","volume":"140","author":"Uddin","year":"2022","journal-title":"Blood"},{"issue":"2","key":"10.1016\/j.tranon.2025.102399_bib0032","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/s41580-019-0173-8","article-title":"Mitochondria as multifaceted regulators of cell death","volume":"21","author":"Bock","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"issue":"1","key":"10.1016\/j.tranon.2025.102399_bib0033","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1038\/cdd.2017.179","article-title":"MOMP, cell suicide as a BCL-2 family business","volume":"25","author":"Kalkavan","year":"2018","journal-title":"Cell. Death. Differ."},{"issue":"1","key":"10.1016\/j.tranon.2025.102399_bib0034","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/cdd.2017.186","article-title":"BCL-2 family proteins: changing partners in the dance towards death","volume":"25","author":"Kale","year":"2018","journal-title":"Cell. Death. Differ."},{"key":"10.1016\/j.tranon.2025.102399_bib0035","doi-asserted-by":"crossref","DOI":"10.1038\/s41580-023-00629-4","article-title":"Mechanisms of BCL-2 family proteins in mitochondrial apoptosis","author":"Czabotar","year":"2023","journal-title":"Nat. Rev. Mol. Cell Biol."},{"issue":"1","key":"10.1016\/j.tranon.2025.102399_bib0036","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.tplants.2016.08.002","article-title":"ROS are good","volume":"22","author":"Mittler","year":"2017","journal-title":"Trends Plant Sci."},{"issue":"3","key":"10.1016\/j.tranon.2025.102399_bib0037","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1152\/physrev.00026.2013","article-title":"Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release","volume":"94","author":"Zorov","year":"2014","journal-title":"Physiol. Rev."},{"issue":"10","key":"10.1016\/j.tranon.2025.102399_bib0038","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1158\/2159-8290.CD-15-0507","article-title":"MYC, metabolism, and cancer","volume":"5","author":"Stine","year":"2015","journal-title":"Cancer Discov."},{"issue":"3","key":"10.1016\/j.tranon.2025.102399_bib0039","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.tcb.2022.07.006","article-title":"MYC: a complex problem","volume":"33","author":"Das","year":"2023","journal-title":"Trends Cell Biol."},{"issue":"1","key":"10.1016\/j.tranon.2025.102399_bib0040","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.cell.2012.03.003","article-title":"MYC on the path to cancer","volume":"149","author":"Dang","year":"2012","journal-title":"Cell"},{"issue":"1","key":"10.1016\/j.tranon.2025.102399_bib0041","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/s41571-021-00549-2","article-title":"The MYC oncogene - the grand orchestrator of cancer growth and immune evasion","volume":"19","author":"Dhanasekaran","year":"2022","journal-title":"Nat. Rev. Clin. Oncol."},{"issue":"9","key":"10.1016\/j.tranon.2025.102399_bib0042","doi-asserted-by":"crossref","first-page":"1864","DOI":"10.1038\/s41418-022-00971-8","article-title":"Deubiquitination of MYC by OTUB1 contributes to HK2 mediated glycolysis and breast tumorigenesis","volume":"29","author":"Han","year":"2022","journal-title":"Cell Death Differ."},{"issue":"1","key":"10.1016\/j.tranon.2025.102399_bib0043","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/s41572-022-00404-3","article-title":"Burkitt lymphoma","volume":"8","author":"L\u00f3pez","year":"2022","journal-title":"Nat. Rev. Dis. Primers"},{"issue":"1","key":"10.1016\/j.tranon.2025.102399_bib0044","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1111\/imr.12734","article-title":"MYC in Germinal Center-derived lymphomas: mechanisms and therapeutic opportunities","volume":"288","author":"Bisso","year":"2019","journal-title":"Immunol. Rev."},{"key":"10.1016\/j.tranon.2025.102399_bib0045","doi-asserted-by":"crossref","DOI":"10.1016\/j.ebiom.2021.103756","article-title":"Therapeutic targeting of \"undruggable\" MYC","volume":"75","author":"Llombart","year":"2022","journal-title":"EBioMedicine."}],"container-title":["Translational Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1936523325001305?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1936523325001305?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T08:31:06Z","timestamp":1778833866000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1936523325001305"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":45,"alternative-id":["S1936523325001305"],"URL":"https:\/\/doi.org\/10.1016\/j.tranon.2025.102399","relation":{},"ISSN":["1936-5233"],"issn-type":[{"value":"1936-5233","type":"print"}],"subject":[],"published":{"date-parts":[[2025,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"The synergy of TPL and selinexor in MLL-R acute myeloid leukemia via Rap1\/Raf\/MEK pathway-mediated MYC downregulation","name":"articletitle","label":"Article Title"},{"value":"Translational Oncology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.tranon.2025.102399","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"102399"}}