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@ARTICLE{Radujkovic:130376,
      author       = {A. Radujkovic and S. Dietrich and M. Andrulis and A.
                      Benner$^*$ and T. Longerich and A. Pellagatti and K. Nanda
                      and T. Giese and U. Germing and S. Baldus and J. Boultwood
                      and A. D. Ho and P. Dreger and T. Luft},
      title        = {{E}xpression of {CDKN}1{C} in the bone marrow of patients
                      with myelodysplastic syndrome and secondary acute myeloid
                      leukemia is associated with poor survival after conventional
                      chemotherapy.},
      journal      = {International journal of cancer},
      volume       = {139},
      number       = {6},
      issn         = {0020-7136},
      address      = {Bognor Regis},
      publisher    = {Wiley-Liss},
      reportid     = {DKFZ-2017-05455},
      pages        = {1402 - 1413},
      year         = {2016},
      abstract     = {We tested the hypothesis that proliferative activity of
                      hematopoietic stem cells has impact on survival in newly
                      diagnosed patients with myelodysplastic syndrome (MDS) and
                      secondary acute myeloid leukemia (AML). RNA expression
                      profiles of CD34(+) cells were analyzed in 125 MDS patients
                      and compared to healthy controls. Prognostic impact on
                      overall survival (OS) of mRNA proliferation signatures
                      established for solid tumor cells was analyzed
                      retrospectively. For validation on the protein level,
                      immunofluorescence and immunohistochemistry analyses in bone
                      marrow (BM) biopsies were performed, and an independent
                      cohort of 223 MDS and secondary AML patients was
                      investigated. Lower proliferative activity correlated with
                      the expression of cyclin-dependent kinase inhibitor 1C
                      (CDKN1C) and with shorter OS (p < 0.001). In
                      multivariable analysis, higher CDKN1C expression was
                      associated with worse OS (p = 0.02). On the BM level, a
                      total of 84 $(38\%)$ patients showed CDKN1C protein
                      expression before start of treatment. Patient, disease and
                      treatment characteristics did not differ between
                      CDKN1C-positive and -negative patients. Positive CDKN1C BM
                      status was associated with shorter OS in multivariable
                      analysis (HR 1.54, p = 0.04). There was an interaction
                      between CDKN1C BM status and subsequent treatment with
                      negative impact on OS being most pronounced in patients
                      receiving conventional cytotoxic chemotherapy (n = 83,
                      2-year OS $30\%$ versus $58\%,$ p = 0.002). In
                      conclusion, low-proliferative phenotype and CDKN1C
                      expression were associated with shorter OS. CDKN1C protein
                      expression in the BM of newly diagnosed, treatment-naïve
                      MDS and secondary AML patients was identified as a
                      prognostic factor for poor survival in patients treated with
                      antiproliferative chemotherapy.},
      keywords     = {Antigens, CD34 (NLM Chemicals) / Biomarkers (NLM Chemicals)
                      / CDKN1C protein, human (NLM Chemicals) / Cyclin-Dependent
                      Kinase Inhibitor p57 (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:27170453},
      doi          = {10.1002/ijc.30181},
      url          = {https://inrepo02.dkfz.de/record/130376},
}