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@ARTICLE{Stein:307371,
      author       = {C. M. Stein and R. Hablesreiter and F. Christen and P.
                      Löwe and C. Fustero-Torre and K. Kopp and B. N. Locher and
                      L. Nitsch and R. Altwasser and J. F. Kerschbaum and L.
                      Bullinger$^*$ and L. S. Ludwig and P. M. Strzelecka and F.
                      Damm$^*$},
      title        = {{D}ynamics of clonal hematopoiesis and cellular responses
                      to stress-induced toxicity in autologous stem cell
                      transplantation.},
      journal      = {Leukemia},
      volume       = {nn},
      issn         = {0887-6924},
      address      = {London},
      publisher    = {Springer Nature},
      reportid     = {DKFZ-2025-03015},
      pages        = {nn},
      year         = {2025},
      note         = {epub},
      abstract     = {Autologous stem cell transplantation (ASCT) involves
                      harvesting hematopoietic stem and progenitor cells (HSPCs)
                      prior to chemotherapy and subsequent repopulation of the
                      bone marrow. This process imposes a bottleneck, providing a
                      framework to dissect the unresolved short- and long-term
                      clonal dynamics during hematopoietic reconstitution. By
                      integrating bulk error-corrected targeted sequencing of
                      clonal hematopoiesis (CH)-associated genes with
                      mitochondrial single-cell Assay for Transposase-Accessible
                      Chromatin sequencing (mtscATAC-seq), we characterized
                      mutational trajectories in frequently altered hematological
                      genes and traced clonal evolution through somatic
                      mitochondrial DNA variants, revealing post-transplant
                      cellular heterogeneity and clonal architecture. Among 60
                      patients (multiple myeloma, n = 51; non-Hodgkin lymphoma, n
                      = 6; Hodgkin lymphoma, n = 3), CH-associated mutations were
                      identified in $53\%$ pre-ASCT, predominantly involving
                      DNMT3A. A transient increase in mutation counts and gene
                      diversity occurred 10-25 days post-ASCT, with a gradual
                      clonal expansion two years post-transplantation. Tandem ASCT
                      amplified clonal complexity, with a twofold increase in
                      mutation count and gene-level diversity, while preserving
                      clonal trajectories across both transplant courses.
                      Mitochondrial single-cell profiling in longitudinal samples
                      of 3 patients showed patient-specific immune reconstitution
                      and clonal dynamics, with balanced multilineage output from
                      graft HSPCs. Collectively, our findings provide a firsthand
                      comprehensive view of ASCT-induced clonal dynamics and
                      immune reconstitution, paving the way for targeted
                      gene-specific post-transplant monitoring.},
      cin          = {BE01},
      ddc          = {610},
      cid          = {I:(DE-He78)BE01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41419602},
      doi          = {10.1038/s41375-025-02823-z},
      url          = {https://inrepo02.dkfz.de/record/307371},
}