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@ARTICLE{Pastoors:290235,
      author       = {D. Pastoors and M. Havermans and R. Mulet-Lazaro and D.
                      Brian and W. Noort and J. Gräsel$^*$ and R. Hoogenboezem
                      and L. Smeenk and J. A. A. Demmers and M. Milsom$^*$ and T.
                      Enver and R. W. J. Groen and E. Bindels and R. Delwel},
      title        = {{O}ncogene {EVI}1 drives acute myeloid leukemia via a
                      targetable interaction with {CTBP}2.},
      journal      = {Science advances},
      volume       = {10},
      number       = {20},
      issn         = {2375-2548},
      address      = {Washington, DC [u.a.]},
      publisher    = {Assoc.},
      reportid     = {DKFZ-2024-01051},
      pages        = {eadk9076},
      year         = {2024},
      abstract     = {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.},
      keywords     = {Leukemia, Myeloid, Acute: genetics / Leukemia, Myeloid,
                      Acute: metabolism / Leukemia, Myeloid, Acute: pathology /
                      MDS1 and EVI1 Complex Locus Protein: metabolism / MDS1 and
                      EVI1 Complex Locus Protein: genetics / Alcohol
                      Oxidoreductases: metabolism / Alcohol Oxidoreductases:
                      genetics / Humans / Animals / DNA-Binding Proteins:
                      metabolism / DNA-Binding Proteins: genetics / Mice /
                      Co-Repressor Proteins: metabolism / Co-Repressor Proteins:
                      genetics / Protein Binding / Cell Line, Tumor / Cell
                      Proliferation / Cell Transformation, Neoplastic: genetics /
                      Cell Transformation, Neoplastic: metabolism / Transcription
                      Factors: metabolism / Transcription Factors: genetics},
      cin          = {A012},
      ddc          = {500},
      cid          = {I:(DE-He78)A012-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:38748792},
      doi          = {10.1126/sciadv.adk9076},
      url          = {https://inrepo02.dkfz.de/record/290235},
}