% 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{Andersson:142742,
      author       = {E. I. Andersson and S. Pützer and B. Yadav and O. Dufva
                      and S. Khan and L. He and L. Sellner$^*$ and A. Schrader and
                      G. Crispatzu and M. Oleś and H. Zhang and S. Adnan-Awad and
                      S. Lagström and D. Bellanger and J. P. Mpindi and S.
                      Eldfors and T. Pemovska and P. Pietarinen and A. Lauhio and
                      K. Tomska$^*$ and C. Cuesta-Mateos and E. Faber and S.
                      Koschmieder and T. H. Brümmendorf and S. Kytölä and E.-R.
                      Savolainen and T. Siitonen and P. Ellonen and O. Kallioniemi
                      and K. Wennerberg and W. Ding and M.-H. Stern and W. Huber
                      and S. Anders and J. Tang and T. Aittokallio and T. Zenz$^*$
                      and M. Herling and S. Mustjoki},
      title        = {{D}iscovery of novel drug sensitivities in {T}-{PLL} by
                      high-throughput ex vivo drug testing and mutation
                      profiling.},
      journal      = {Leukemia},
      volume       = {32},
      number       = {3},
      issn         = {1476-5551},
      address      = {London},
      publisher    = {Springer Nature},
      reportid     = {DKFZ-2019-00459},
      pages        = {774 - 787},
      year         = {2018},
      abstract     = {T-cell prolymphocytic leukemia (T-PLL) is a rare and
                      aggressive neoplasm of mature T-cells with an urgent need
                      for rationally designed therapies to address its notoriously
                      chemo-refractory behavior. The median survival of T-PLL
                      patients is <2 years and clinical trials are difficult to
                      execute. Here we systematically explored the diversity of
                      drug responses in T-PLL patient samples using an ex vivo
                      drug sensitivity and resistance testing platform and
                      correlated the findings with somatic mutations and gene
                      expression profiles. Intriguingly, all T-PLL samples were
                      sensitive to the cyclin-dependent kinase inhibitor SNS-032,
                      which overcame stromal-cell-mediated protection and elicited
                      robust p53-activation and apoptosis. Across all patients,
                      the most effective classes of compounds were histone
                      deacetylase, phosphoinositide-3 kinase/AKT/mammalian target
                      of rapamycin, heat-shock protein 90 and BH3-family protein
                      inhibitors as well as p53 activators, indicating previously
                      unexplored, novel targeted approaches for treating T-PLL.
                      Although Janus-activated kinase-signal transducer and
                      activator of transcription factor (JAK-STAT) pathway
                      mutations were common in T-PLL $(71\%$ of patients),
                      JAK-STAT inhibitor responses were not directly linked to
                      those or other T-PLL-specific lesions. Overall, we found
                      that genetic markers do not readily translate into novel
                      effective therapeutic vulnerabilities. In conclusion, novel
                      classes of compounds with high efficacy in T-PLL were
                      discovered with the comprehensive ex vivo drug screening
                      platform warranting further studies of synergisms and
                      clinical testing.},
      keywords     = {Antineoplastic Agents (NLM Chemicals) / Biomarkers, Tumor
                      (NLM Chemicals) /
                      N-(5-(((5-(1,1-dimethylethyl)-2-oxazolyl)methyl)thio)-2-thiazolyl)-4-piperidinecarboxamide
                      (NLM Chemicals) / Oxazoles (NLM Chemicals) / Protein Kinase
                      Inhibitors (NLM Chemicals) / STAT Transcription Factors (NLM
                      Chemicals) / Thiazoles (NLM Chemicals) / Janus Kinases (NLM
                      Chemicals)},
      cin          = {G100 / G250},
      ddc          = {610},
      cid          = {I:(DE-He78)G100-20160331 / I:(DE-He78)G250-20160331},
      pnm          = {317 - Translational cancer research (POF3-317)},
      pid          = {G:(DE-HGF)POF3-317},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:28804127},
      doi          = {10.1038/leu.2017.252},
      url          = {https://inrepo02.dkfz.de/record/142742},
}