% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Vasyutina:127693,
      author       = {E. Vasyutina and J. M. Boucas and J. Bloehdorn and C. Aszyk
                      and G. Crispatzu and M. Stiefelhagen and A. Breuer and P.
                      Mayer and C. Lengerke and H. Döhner and D. Beutner and A.
                      Rosenwald and S. Stilgenbauer and M. Hallek and A.
                      Benner$^*$ and M. Herling},
      title        = {{T}he regulatory interaction of {EVI}1 with the {TCL}1{A}
                      oncogene impacts cell survival and clinical outcome in
                      {CLL}.},
      journal      = {Leukemia},
      volume       = {29},
      number       = {10},
      issn         = {1476-5551},
      address      = {Basingstoke},
      publisher    = {Nature Publ. Group},
      reportid     = {DKFZ-2017-03716},
      pages        = {2003 - 2014},
      year         = {2015},
      abstract     = {Dysregulated T-cell leukemia/lymphoma-1A (TCL1A), a
                      modulator in B-cell receptor (BCR) signaling, is causally
                      implicated in chronic lymphocytic leukemia (CLL). However,
                      the mechanisms of the perturbed TCL1A regulation are largely
                      unknown. To characterize TCL1A-upstream networks, we
                      functionally screened for TCL1A-repressive micro-RNAs (miRs)
                      and their transcriptional regulators. We identified the
                      novel miR-484 to target TCL1As 3-UTR and to be downregulated
                      in CLL. In chromatin immunoprecipitations and reporter
                      assays, the oncogenic transcription factor of myeloid cells,
                      EVI1, bound and activated the miR-484 promoter. Most common
                      in CLL was a pan-EVI1 transcript variant. EVI1 protein
                      expression revealed distinct normal-tissue and
                      leukemia-associated patterns of EVI1/TCL1A co-regulation.
                      EVI1 levels were particularly low in TCL1A-high CLL or such
                      cellular subsets. Global gene expression profiles from a
                      337-patient set linked EVI1 networks to BCR signaling and
                      cell survival via TCL1A, BTK and other molecules of
                      relevance in CLL. Enforced EVI1, as did miR-484, repressed
                      TCL1A. Furthermore, it reduced phospho-kinase levels,
                      impaired cell survival, mitigated BCR-induced Ca-flux and
                      diminished the in vitro ibrutinib response. Moreover, TCL1A
                      and EVI1 showed a strongly interactive hazard prediction in
                      prospectively treated patients. Overall, we present
                      regressive EVI1 as a novel regulatory signature in CLL.
                      Through enhanced TCL1A and other EVI1-targeted hallmarks of
                      CLL, this contributes to an aggressive cellular and clinical
                      phenotype.},
      keywords     = {Biomarkers, Tumor (NLM Chemicals) / DNA-Binding Proteins
                      (NLM Chemicals) / MECOM protein, human (NLM Chemicals) /
                      MIRN484 microRNA, human (NLM Chemicals) / MicroRNAs (NLM
                      Chemicals) / Proto-Oncogene Proteins (NLM Chemicals) / RNA,
                      Messenger (NLM Chemicals) / TCL1A protein, human (NLM
                      Chemicals) / Transcription Factors (NLM Chemicals)},
      cin          = {C060},
      ddc          = {610},
      cid          = {I:(DE-He78)C060-20160331},
      pnm          = {313 - Cancer risk factors and prevention (POF3-313)},
      pid          = {G:(DE-HGF)POF3-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:25936528},
      doi          = {10.1038/leu.2015.114},
      url          = {https://inrepo02.dkfz.de/record/127693},
}