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@ARTICLE{Prutsch:141404,
      author       = {N. Prutsch and E. Gurnhofer and T. Suske and H. C. Liang
                      and M. Schlederer and S. Roos and L. C. Wu and I.
                      Simonitsch-Klupp and A. Alvarez-Hernandez and C. Kornauth
                      and D. A. Leone and J. Svinka and R. Eferl and T. Limberger
                      and A. Aufinger and N. Shirsath and P. Wolf and T.
                      Hielscher$^*$ and F. Aberger and J. Schmoellerl and D.
                      Stoiber and B. Strobl and U. Jäger and P. B. Staber and F.
                      Grebien and R. Moriggl and M. Müller and G. G. Inghirami
                      and T. Sanda and A. T. Look and S. D. Turner and L. Kenner
                      and O. Merkel},
      title        = {{D}ependency on the {TYK}2/{STAT}1/{MCL}1 axis in
                      anaplastic large cell lymphoma.},
      journal      = {Leukemia},
      volume       = {33},
      number       = {3},
      issn         = {1476-5551},
      address      = {London},
      publisher    = {Springer Nature},
      reportid     = {DKFZ-2018-01910},
      pages        = {696-709},
      year         = {2019},
      abstract     = {TYK2 is a member of the JAK family of tyrosine kinases that
                      is involved in chromosomal translocation-induced fusion
                      proteins found in anaplastic large cell lymphomas (ALCL)
                      that lack rearrangements activating the anaplastic lymphoma
                      kinase (ALK). Here we demonstrate that TYK2 is highly
                      expressed in all cases of human ALCL, and that in a mouse
                      model of NPM-ALK-induced lymphoma, genetic disruption of
                      Tyk2 delays the onset of tumors and prolongs survival of the
                      mice. Lymphomas in this model lacking Tyk2 have reduced
                      STAT1 and STAT3 phosphorylation and reduced expression of
                      Mcl1, a pro-survival member of the BCL2 family. These
                      findings in mice are mirrored in human ALCL cell lines, in
                      which TYK2 is activated by autocrine production of IL-10 and
                      IL-22 and by interaction with specific receptors expressed
                      by the cells. Activated TYK2 leads to STAT1 and STAT3
                      phosphorylation, activated expression of MCL1 and aberrant
                      ALCL cell survival. Moreover, TYK2 inhibitors are able to
                      induce apoptosis in ALCL cells, regardless of the presence
                      or absence of an ALK-fusion. Thus, TYK2 is a dependency that
                      is required for ALCL cell survival through activation of
                      MCL1 expression. TYK2 represents an attractive drug target
                      due to its essential enzymatic domain, and TYK2-specific
                      inhibitors show promise as novel targeted inhibitors for
                      ALCL.},
      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:30131584},
      doi          = {10.1038/s41375-018-0239-1},
      url          = {https://inrepo02.dkfz.de/record/141404},
}