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@ARTICLE{Karpova:299795,
      author       = {D. Karpova$^*$ and H. Huerga Encabo and E. Donato$^*$ and
                      S. Calderazzo$^*$ and M. Scherer$^*$ and M. Llorian-Sopena
                      and A.-M. Leppä$^*$ and R. Würth$^*$ and P. Stelmach$^*$
                      and D. Papazoglou and A. Ferrelli and S. Ngo and I. Kotova
                      and S. Harenkamp and K. Zimmer and D. Wolf and J. Panten$^*$
                      and J. Reed and A. Przybylla$^*$ and T. Tonn and A.
                      Kopp-Schneider$^*$ and L. Velten and J. F. DiPersio and T.
                      N. Wong and D. Bonnet and H. Bonig and A. Trumpp$^*$},
      title        = {{C}lonal {H}ematopoiesis {L}andscape in {F}requent {B}lood
                      {D}onors.},
      journal      = {Blood},
      volume       = {145},
      number       = {21},
      issn         = {0006-4971},
      address      = {Washington, DC},
      publisher    = {American Society of Hematology},
      reportid     = {DKFZ-2025-00550},
      pages        = {2411-2423},
      year         = {2025},
      note         = {DKFZ- ZMBH Alliance / #EA:A010#LA:A010# / 2025 May
                      22;145(21):2411-2423},
      abstract     = {Donor blood saves lives, yet the potential impact of
                      recurrent large-volume phlebotomy on donor health and
                      hematopoietic stem cells (HSCs) remains largely unexplored.
                      In our study, we conducted a comprehensive screening of 217
                      older male volunteer donors with a history of extensive
                      blood donation (>100 life-time donations) to investigate the
                      phenomenon of clonal hematopoiesis (CH). No significant
                      difference in the overall incidence of CH was found in
                      frequent donors (FD) compared to sporadic donors (<10
                      life-time donations, 212 donors). However, upon deeper
                      analysis of mutations in DNMT3A, the most commonly affected
                      gene in CH, we observed distinct mutational patterns between
                      the FD and age/sex matched control donor (CD) cohorts.
                      Functional analysis of FD enriched DNMT3A variants examined
                      in CRISPR-edited human HSCs demonstrated their competitive
                      outgrowth potential upon stimulation with erythropoietin
                      (EPO), a hormone which increases in response to blood loss.
                      In contrast, clones harboring leukemogenic DNMT3A R882
                      mutations increase upon stimulation with IFNy. Through
                      concurrent mutational and immunophenotypic profiling of
                      primary samples at single cell resolution, a myeloid bias of
                      premalignant R882 mutant HSCs was found, while no
                      significant lineage bias was observed in HSCs harboring EPO
                      responsive DNMT3A variants. The latter exhibited
                      preferential erythroid differentiation when persistent
                      erythropoietic stress was applied to CRISPR-edited human HSC
                      xenografts. Our data demonstrate a nuanced ongoing Darwinian
                      evolution at the somatic stem cell level, with EPO
                      identified as a novel environmental factor that favors HSCs
                      carrying certain DNMT3A mutations.},
      cin          = {A010 / C060 / B370 / B270 / HD01},
      ddc          = {610},
      cid          = {I:(DE-He78)A010-20160331 / I:(DE-He78)C060-20160331 /
                      I:(DE-He78)B370-20160331 / I:(DE-He78)B270-20160331 /
                      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:40067117},
      doi          = {10.1182/blood.2024027999},
      url          = {https://inrepo02.dkfz.de/record/299795},
}