% 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{Stelmach:277279,
      author       = {P. Stelmach$^*$ and S. Richter and S. Sauer and M. A. Fabre
                      and M. Gu and C. Rohde and M. Janssen and N. Liebers and R.
                      Proynova and N. Weinhold and M. S. Raab and H. Goldschmidt
                      and B. Besenbeck and P. Pavel and S. Laier and A. Trumpp$^*$
                      and S. Dietrich and G. S. Vassiliou and C. Müller-Tidow},
      title        = {{C}lonal hematopoiesis with {DNMT}3{A} and {PPM}1{D}
                      mutations impairs regeneration in autologous stem cell
                      transplant recipients.},
      journal      = {Haematologica},
      volume       = {108},
      number       = {12},
      issn         = {0390-6078},
      address      = {Pavia},
      publisher    = {Ferrata Storti Foundation},
      reportid     = {DKFZ-2023-01313},
      pages        = {3308-3320},
      year         = {2023},
      note         = {DKFZ-ZMBH Alliance / 2023 Dec 1;108(12):3308-3320 /
                      #EA:A010#},
      abstract     = {Clonal hematopoiesis (CH) is an age-related condition
                      driven by stem- and progenitor cells harboring recurrent
                      mutations linked to myeloid neoplasms. Currently, potential
                      effects on hematopoiesis, stem cell function and
                      regenerative potential under stress conditions are unknown.
                      We performed targeted DNA sequencing of 457 hematopoietic
                      stem cell grafts collected for autologous stem cell
                      transplantation (ASCT) in myeloma patients and correlated
                      our findings with high-dimensional longitudinal clinical and
                      laboratory data (26,510 data points for blood cell
                      counts/serum values in 25 days around transplantation). We
                      detected CH-related mutations in 152 patients $(33.3\%).$
                      Since many patients (n = 54) harbored multiple CH mutations
                      in one or more genes, we applied a non-negative matrix
                      factorization (NMF) clustering algorithm to identify genes
                      that are commonly co-mutated in an unbiased approach.
                      Patients with CH were assigned to one of three clusters
                      (C1-C3) and compared to patients without CH (C0) in a gene
                      specific manner. To study the dynamics of blood cell
                      regeneration following ASCT, we developed a time-dependent
                      linear mixed effect model to validate differences in blood
                      cell count trajectories amongst different clusters. The
                      results demonstrated that C2, composed of patients with
                      DNMT3A and PPM1D single and comutated CH, correlated with
                      reduced stem cell yields and delayed platelet count recovery
                      following ASCT. Also, the benefit of maintenance therapy was
                      particularly strong in C2 patients. Taken together, these
                      data indicate an impaired regenerative potential of
                      hematopoietic stem cell grafts harboring CH with DNMT3A and
                      PPM1D mutations.},
      cin          = {A010 / HD01},
      ddc          = {610},
      cid          = {I:(DE-He78)A010-20160331 / I:(DE-He78)HD01-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37381752},
      doi          = {10.3324/haematol.2023.282992},
      url          = {https://inrepo02.dkfz.de/record/277279},
}