Home > Publications database > Oncogene EVI1 drives acute myeloid leukemia via a targetable interaction with CTBP2. > print

001     290235
005     20240519011238.0
024 7 _ |a 10.1126/sciadv.adk9076
|2 doi
024 7 _ |a pmid:38748792
|2 pmid
024 7 _ |a altmetric:163401383
|2 altmetric
037 _ _ |a DKFZ-2024-01051
041 _ _ |a English
082 _ _ |a 500
100 1 _ |a Pastoors, Dorien
|0 0000-0002-5322-1961
|b 0
245 _ _ |a Oncogene EVI1 drives acute myeloid leukemia via a targetable interaction with CTBP2.
260 _ _ |a Washington, DC [u.a.]
|c 2024
|b Assoc.
336 7 _ |a article
|2 DRIVER
336 7 _ |a Output Types/Journal article
|2 DataCite
336 7 _ |a Journal Article
|b journal
|m journal
|0 PUB:(DE-HGF)16
|s 1715954531_22132
|2 PUB:(DE-HGF)
336 7 _ |a ARTICLE
|2 BibTeX
336 7 _ |a JOURNAL_ARTICLE
|2 ORCID
336 7 _ |a Journal Article
|0 0
|2 EndNote
520 _ _ |a Acute myeloid leukemia (AML) driven by the activation of EVI1 due to chromosome 3q26/MECOM 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× PLDLS repeat construct outcompetes binding of EVI1 to CTBP1 and CTBP2 and inhibits proliferation of 3q26/MECOM 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.
536 _ _ |a 311 - Zellbiologie und Tumorbiologie (POF4-311)
|0 G:(DE-HGF)POF4-311
|c POF4-311
|f POF IV
|x 0
588 _ _ |a Dataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de
650 _ 2 |a Leukemia, Myeloid, Acute: genetics
|2 MeSH
650 _ 2 |a Leukemia, Myeloid, Acute: metabolism
|2 MeSH
650 _ 2 |a Leukemia, Myeloid, Acute: pathology
|2 MeSH
650 _ 2 |a MDS1 and EVI1 Complex Locus Protein: metabolism
|2 MeSH
650 _ 2 |a MDS1 and EVI1 Complex Locus Protein: genetics
|2 MeSH
650 _ 2 |a Alcohol Oxidoreductases: metabolism
|2 MeSH
650 _ 2 |a Alcohol Oxidoreductases: genetics
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a DNA-Binding Proteins: metabolism
|2 MeSH
650 _ 2 |a DNA-Binding Proteins: genetics
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Co-Repressor Proteins: metabolism
|2 MeSH
650 _ 2 |a Co-Repressor Proteins: genetics
|2 MeSH
650 _ 2 |a Protein Binding
|2 MeSH
650 _ 2 |a Cell Line, Tumor
|2 MeSH
650 _ 2 |a Cell Proliferation
|2 MeSH
650 _ 2 |a Cell Transformation, Neoplastic: genetics
|2 MeSH
650 _ 2 |a Cell Transformation, Neoplastic: metabolism
|2 MeSH
650 _ 2 |a Transcription Factors: metabolism
|2 MeSH
650 _ 2 |a Transcription Factors: genetics
|2 MeSH
700 1 _ |a Havermans, Marije
|0 0009-0009-7996-9458
|b 1
700 1 _ |a Mulet-Lazaro, Roger
|0 0000-0003-0298-7948
|b 2
700 1 _ |a Brian, Duncan
|0 0000-0002-3980-7341
|b 3
700 1 _ |a Noort, Willy
|0 0009-0007-0943-8729
|b 4
700 1 _ |a Gräsel, Julius
|0 P:(DE-He78)f3428d5eb2ce372b596cca4354cbfaa8
|b 5
700 1 _ |a Hoogenboezem, Remco
|b 6
700 1 _ |a Smeenk, Leonie
|0 0000-0001-7025-8515
|b 7
700 1 _ |a Demmers, Jeroen A A
|0 0000-0002-8757-9611
|b 8
700 1 _ |a Milsom, Michael
|0 P:(DE-He78)7b613cadb8c16ce178713e15b85d982c
|b 9
|u dkfz
700 1 _ |a Enver, Tariq
|b 10
700 1 _ |a Groen, Richard W J
|0 0000-0002-5010-4604
|b 11
700 1 _ |a Bindels, Eric
|0 0000-0001-9502-669X
|b 12
700 1 _ |a Delwel, Ruud
|b 13
773 _ _ |a 10.1126/sciadv.adk9076
|g Vol. 10, no. 20, p. eadk9076
|0 PERI:(DE-600)2810933-8
|n 20
|p eadk9076
|t Science advances
|v 10
|y 2024
|x 2375-2548
909 C O |o oai:inrepo02.dkfz.de:290235
|p VDB
910 1 _ |a Deutsches Krebsforschungszentrum
|0 I:(DE-588b)2036810-0
|k DKFZ
|b 5
|6 P:(DE-He78)f3428d5eb2ce372b596cca4354cbfaa8
910 1 _ |a Deutsches Krebsforschungszentrum
|0 I:(DE-588b)2036810-0
|k DKFZ
|b 9
|6 P:(DE-He78)7b613cadb8c16ce178713e15b85d982c
913 1 _ |a DE-HGF
|b Gesundheit
|l Krebsforschung
|1 G:(DE-HGF)POF4-310
|0 G:(DE-HGF)POF4-311
|3 G:(DE-HGF)POF4
|2 G:(DE-HGF)POF4-300
|4 G:(DE-HGF)POF
|v Zellbiologie und Tumorbiologie
|x 0
914 1 _ |y 2024
915 _ _ |a JCR
|0 StatID:(DE-HGF)0100
|2 StatID
|b SCI ADV : 2022
|d 2023-08-28
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0200
|2 StatID
|b SCOPUS
|d 2023-08-28
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0300
|2 StatID
|b Medline
|d 2023-08-28
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0320
|2 StatID
|b PubMed Central
|d 2023-08-28
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0501
|2 StatID
|b DOAJ Seal
|d 2021-09-20T13:50:30Z
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0500
|2 StatID
|b DOAJ
|d 2021-09-20T13:50:30Z
915 _ _ |a Peer Review
|0 StatID:(DE-HGF)0030
|2 StatID
|b DOAJ : Anonymous peer review
|d 2021-09-20T13:50:30Z
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0600
|2 StatID
|b Ebsco Academic Search
|d 2023-08-28
915 _ _ |a Peer Review
|0 StatID:(DE-HGF)0030
|2 StatID
|b ASC
|d 2023-08-28
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0199
|2 StatID
|b Clarivate Analytics Master Journal List
|d 2023-08-28
915 _ _ |a WoS
|0 StatID:(DE-HGF)0113
|2 StatID
|b Science Citation Index Expanded
|d 2023-08-28
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0150
|2 StatID
|b Web of Science Core Collection
|d 2023-08-28
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1040
|2 StatID
|b Zoological Record
|d 2023-08-28
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0160
|2 StatID
|b Essential Science Indicators
|d 2023-08-28
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1150
|2 StatID
|b Current Contents - Physical, Chemical and Earth Sciences
|d 2023-08-28
915 _ _ |a IF >= 10
|0 StatID:(DE-HGF)9910
|2 StatID
|b SCI ADV : 2022
|d 2023-08-28
915 _ _ |a Article Processing Charges
|0 StatID:(DE-HGF)0561
|2 StatID
|d 2023-08-28
915 _ _ |a Fees
|0 StatID:(DE-HGF)0700
|2 StatID
|d 2023-08-28
920 1 _ |0 I:(DE-He78)A012-20160331
|k A012
|l A012 Experimentelle Hämatologie
|x 0
980 _ _ |a journal
980 _ _ |a VDB
980 _ _ |a I:(DE-He78)A012-20160331
980 _ _ |a UNRESTRICTED

LibraryCollectionCLSMajorCLSMinorLanguageAuthor
Marc 21