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@ARTICLE{Jahn:181024,
      author       = {N. Jahn and E. Jahn and M. Saadati and L. Bullinger and R.
                      A. Larson and T. Ottone and S. Amadori and T. W. Prior and
                      J. M. Brandwein and F. R. Appelbaum and B. C. Medeiros and
                      M. S. Tallman and G. Ehninger and M. Heuser and A. Ganser
                      and C. Pallaud and I. Gathmann and J. Krzykalla$^*$ and A.
                      Benner$^*$ and C. D. Bloomfield and C. Thiede and R. M.
                      Stone and H. Döhner and K. Döhner},
      title        = {{G}enomic landscape of patients with {FLT}3-mutated acute
                      myeloid leukemia ({AML}) treated within the {CALGB}
                      10603/{RATIFY} trial.},
      journal      = {Leukemia},
      volume       = {36},
      number       = {9},
      issn         = {0887-6924},
      address      = {London},
      publisher    = {Springer Nature},
      reportid     = {DKFZ-2022-01731},
      pages        = {2218-2227},
      year         = {2022},
      note         = {2022 Sep;36(9):2218-2227},
      abstract     = {The aim of this study was to characterize the mutational
                      landscape of patients with FLT3-mutated acute myeloid
                      leukemia (AML) treated within the randomized CALGB
                      10603/RATIFY trial evaluating intensive chemotherapy plus
                      the multi-kinase inhibitor midostaurin versus placebo. We
                      performed sequencing of 262 genes in 475 patients: mutations
                      occurring concurrently with the FLT3-mutation were most
                      frequent in NPM1 $(61\%),$ DNMT3A $(39\%),$ WT1 $(21\%),$
                      TET2 $(12\%),$ NRAS $(11\%),$ RUNX1 $(11\%),$ PTPN11
                      $(10\%),$ and ASXL1 $(8\%)$ genes. To assess effects of
                      clinical and genetic features and their possible
                      interactions, we fitted random survival forests and
                      interpreted the resulting variable importance. Highest
                      prognostic impact was found for WT1 and NPM1 mutations,
                      followed by white blood cell count, FLT3 mutation type
                      (internal tandem duplications vs. tyrosine kinase domain
                      mutations), treatment (midostaurin vs. placebo), ASXL1
                      mutation, and ECOG performance status. When evaluating
                      two-fold variable combinations the most striking effects
                      were found for WT1:NPM1 (with NPM1 mutation abrogating the
                      negative effect of WT1 mutation), and for WT1:treatment
                      (with midostaurin exerting a beneficial effect in
                      WT1-mutated AML). This targeted gene sequencing study
                      provides important, novel insights into the genomic
                      background of FLT3-mutated AML including the prognostic
                      impact of co-mutations, specific gene-gene interactions, and
                      possible treatment effects of midostaurin.},
      cin          = {C060},
      ddc          = {610},
      cid          = {I:(DE-He78)C060-20160331},
      pnm          = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
      pid          = {G:(DE-HGF)POF4-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:35922444},
      doi          = {10.1038/s41375-022-01650-w},
      url          = {https://inrepo02.dkfz.de/record/181024},
}