{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T10:16:10Z","timestamp":1791886570460,"version":"4.3.4"},"reference-count":53,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"20","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2024,5,17]]},"abstract":"<jats:p>\n                    Acute myeloid leukemia (AML) driven by the activation of\n                    <jats:italic>EVI1<\/jats:italic>\n                    due to chromosome 3q26\/\n                    <jats:italic>MECOM<\/jats:italic>\n                    rearrangements is incurable. Because transcription factors such as EVI1 are notoriously hard to target, insight into the mechanism by which EVI1 drives myeloid transformation could provide alternative avenues for therapy. Applying protein folding predictions combined with proteomics technologies, we demonstrate that interaction of EVI1 with CTBP1 and CTBP2 via a single PLDLS motif is indispensable for leukemic transformation. A 4\u00d7 PLDLS repeat construct outcompetes binding of EVI1 to CTBP1 and CTBP2 and inhibits proliferation of 3q26\/\n                    <jats:italic>MECOM<\/jats:italic>\n                    rearranged AML in vitro and in xenotransplant models. This proof-of-concept study opens the possibility to target one of the most incurable forms of AML with specific EVI1-CTBP inhibitors. This has important implications for other tumor types with aberrant expression of EVI1 and for cancers transformed by different CTBP-dependent oncogenic transcription factors.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adk9076","type":"journal-article","created":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T14:00:27Z","timestamp":1715781627000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":19,"title":["Oncogene\n                    <i>EVI1<\/i>\n                    drives acute myeloid leukemia via a targetable interaction with CTBP2"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5322-1961","authenticated-orcid":true,"given":"Dorien","family":"Pastoors","sequence":"first","affiliation":[{"name":"Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, Netherlands."},{"name":"Oncode Institute, Utrecht, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7996-9458","authenticated-orcid":true,"given":"Marije","family":"Havermans","sequence":"additional","affiliation":[{"name":"Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, Netherlands."},{"name":"Oncode Institute, Utrecht, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0298-7948","authenticated-orcid":true,"given":"Roger","family":"Mulet-Lazaro","sequence":"additional","affiliation":[{"name":"Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, Netherlands."},{"name":"Oncode Institute, Utrecht, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3980-7341","authenticated-orcid":true,"given":"Duncan","family":"Brian","sequence":"additional","affiliation":[{"name":"Stem Cell Group, UCL Cancer Institute, University College London, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0943-8729","authenticated-orcid":true,"given":"Willy","family":"Noort","sequence":"additional","affiliation":[{"name":"Department of Hematology, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam, Netherlands."},{"name":"Cancer Center Amsterdam, Cancer biology and immunology, Amsterdam, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julius","family":"Grasel","sequence":"additional","affiliation":[{"name":"Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120 Heidelberg, Germany."},{"name":"Division of Experimental Hematology, German Cancer Research Center, DKFZ69120 Heidelberg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Remco","family":"Hoogenboezem","sequence":"additional","affiliation":[{"name":"Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7025-8515","authenticated-orcid":true,"given":"Leonie","family":"Smeenk","sequence":"additional","affiliation":[{"name":"Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, Netherlands."},{"name":"Oncode Institute, Utrecht, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8757-9611","authenticated-orcid":true,"given":"Jeroen A. A.","family":"Demmers","sequence":"additional","affiliation":[{"name":"Proteomics Center, Erasmus MC, Rotterdam, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3567-254X","authenticated-orcid":true,"given":"Michael D.","family":"Milsom","sequence":"additional","affiliation":[{"name":"Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120 Heidelberg, Germany."},{"name":"Division of Experimental Hematology, German Cancer Research Center, DKFZ69120 Heidelberg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tariq","family":"Enver","sequence":"additional","affiliation":[{"name":"Stem Cell Group, UCL Cancer Institute, University College London, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5010-4604","authenticated-orcid":true,"given":"Richard W. J.","family":"Groen","sequence":"additional","affiliation":[{"name":"Department of Hematology, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam, Netherlands."},{"name":"Cancer Center Amsterdam, Cancer biology and immunology, Amsterdam, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9502-669X","authenticated-orcid":true,"given":"Eric","family":"Bindels","sequence":"additional","affiliation":[{"name":"Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6903-3271","authenticated-orcid":true,"given":"Ruud","family":"Delwel","sequence":"additional","affiliation":[{"name":"Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, Netherlands."},{"name":"Oncode Institute, Utrecht, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1516192"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019003701"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.02.019"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-20-1793"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2014.02.008"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-11-393827"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-022-01370-4"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205436"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.06.048"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.9.2815"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1192"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1309310110"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/27945"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2008.06.056"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi800267f"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M106733200"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkj109"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2001.02987.x"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1039\/D1MO00236H"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac1015"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.71.9.6796-6804.1997"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0437-z"},{"key":"e_1_3_2_24_2","first-page":"18","article-title":"S117: EVI1 drives leukemogenesis through aberrant ERG activation","volume":"6","author":"Schmoellerl J.","year":"2022","unstructured":"J. Schmoellerl, I. Barbosa, M. Minnich, F. Andersch, L. Smeenk, M. Havermans, T. Eder, T. Neumann, J. Jude, M. Fellner, A. Ebert, M. Steininger, R. Delwel, F. Grebien, J. Zuber, S117: EVI1 drives leukemogenesis through aberrant ERG activation. Blood 6, 18\u201319 (2022).","journal-title":"Blood"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03819-2"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M102343200"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2011.11.001"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-03-414920"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2016.108"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-020-05829-1"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/17.17.5129"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/1878-0261.12330"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(02)00650-0"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2014.03.026"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.11.111"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-26638-5"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkh344"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0145-2126(96)00132-4"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.20153"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-11-122119"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201744993"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2016.136"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2017.147"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2009-10-3-r25"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2008-9-9-r137"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu775"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10730"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-3578-9_16"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.152140.112"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-11-237"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv494"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-05-719021"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-02-204396"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00445-06"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.adk9076","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T14:00:56Z","timestamp":1715781656000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.adk9076"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,17]]},"references-count":53,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2024,5,17]]}},"alternative-id":["10.1126\/sciadv.adk9076"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.adk9076","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.07.11.548358","asserted-by":"object"}]},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,17]]},"assertion":[{"value":"2023-09-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadk9076"}}