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@ARTICLE{Mecklenbrauck:309803,
      author       = {R. Mecklenbrauck and A. Villaverde Ramiro and E. Sträng
                      and R. Gabdoulline and J. Martinez Elicegui and M. Sobas and
                      L. Pleyer and A. Turki and M. T. Voso and A. Benner$^*$ and
                      A. Hernández-Sánchez and J. M. Tettero and L. Tur Gimenez
                      and K. H. Metzeler and G. Oñate and S. Lehmann and B. J.
                      Huntly and I. Thomas and F. R. Thol and F. H. Heidel and P.
                      J. Valk and K. Döhner and T. Haferlach and K. I. Mills and
                      H. Döhner and G. Castellani and G. J. Ossenkoppele and J.
                      M. Hernández-Rivas and L. Bullinger and M. Heuser},
      title        = {{P}rognostic impact of myelodysplasia-related gene
                      mutations in {FLT}3-{ITD}-mutated acute myeloid leukemia.},
      journal      = {Leukemia},
      volume       = {nn},
      issn         = {0887-6924},
      address      = {London},
      publisher    = {Springer Nature},
      reportid     = {DKFZ-2026-00316},
      pages        = {nn},
      year         = {2026},
      note         = {epub},
      abstract     = {The inclusion of nine myelodysplasia-related gene (MRG)
                      mutations (ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2,
                      U2AF1, ZRSR2) as adverse risk factors in the ELN risk
                      classification has reshaped classification in acute myeloid
                      leukemia (AML). AML with FLT3-ITD mutations and co-occurring
                      MRG alterations is now classified to the ELN adverse risk
                      group although supporting evidence remains limited. Among
                      4,078 patients with AML with available molecular information
                      included in the HARMONY platform, 862 harbored FLT3-ITD
                      mutations and underwent intensive chemotherapy. Of these,
                      171 $(20\%)$ exhibited co-occurring MRG mutations at
                      diagnosis. In this cohort, MRGs were not independently
                      associated with relapse-free survival (RFS) or overall
                      survival (OS). In the FLT3-ITD/NPM1 co-mutated subgroup, MRG
                      mutations were rare $(9\%)$ and showed no prognostic impact.
                      Conversely, in FLT3-ITD/NPM1 wildtype AML, MRG mutations
                      were predictive of shorter RFS (HR 1.37, $95\%CI$ 1.01 -
                      1.88, p = 0.046) and OS (HR 1.34, $95\%CI$ 1.02-1.74, p =
                      0.032) in multivariable analysis with survival times
                      comparable to the ELN adverse risk category. The allelic
                      ratio of FLT3-ITD did not further stratify OS and RFS in
                      this subgroup. These findings suggest that the prognostic
                      relevance of MRG mutations in FLT3-ITD AML is modulated by
                      NPM1 co-mutational status and mirror findings in AML lacking
                      FLT3-ITD.},
      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:41663622},
      doi          = {10.1038/s41375-026-02874-w},
      url          = {https://inrepo02.dkfz.de/record/309803},
}