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@ARTICLE{Baumhardt:306342,
      author       = {T. M. Baumhardt and A. Amoah and M. Hoenicka and A. Liebold
                      and V. Sakk and K. Soller and A. Vollmer and M. Kull and J.
                      Kronke and J.-P. Mallm$^*$ and H. Geiger and M. Mulaw},
      title        = {{F}unctional and molecular analyses reveal impaired {HSPC}s
                      in {M}ultiple {M}yeloma patients post-induction.},
      journal      = {Stem cells translational medicine},
      volume       = {14},
      number       = {11},
      issn         = {2157-6564},
      address      = {Oxford},
      publisher    = {Oxford University Press},
      reportid     = {DKFZ-2025-02558},
      pages        = {szaf061},
      year         = {2025},
      abstract     = {High-dose chemotherapy and consecutive autologous stem cell
                      transplantation (ASCT) remain the backbone of treatment for
                      transplant-eligible patients of Multiple Myeloma (MM).
                      However, patients are still at high risk of relapse or
                      treatment-related complications. Hence, by understanding the
                      function of hematopoietic stem and progenitor cells (HSPCs)
                      from MM patients in more detail, transplant outcomes in MM
                      patients might be further improved. We combine in our study
                      functional analyses of the potential of HSPCs from newly
                      diagnosed (NDMM) and chemotherapy treated MM patients in a
                      xenotransplant model system with in depth single cells
                      sequencing analysis to provide novel data that might inform
                      clinical routine to improve the outcome of ASCT in MM. Our
                      data demonstrate that (i) HSPCs from treated MM patients are
                      indeed significantly impaired in their overall
                      reconstitution potential and provide a reduced level of
                      B-cells in comparison to HSPCs from age-matched healthy
                      donors and NDMM patients. (ii) We further demonstrate that
                      CD34+ HSPCs acquire a high-risk MM expression profile
                      signature upon induction treatment, which likely adds to the
                      risk of relapse. This high-risk MM expression profile
                      signature relies within CD34+ HSPCs primarily in
                      granulocyte/macrophage progenitors (GMPs), megakaryocyte
                      Erythroid Progenitors (MEPs) and monocytes, while
                      hematopoietic stem cells (HSCs) stay unaffected by
                      transcriptional changes. These data suggest that the
                      elimination of myeloid progenitors and more mature monocytes
                      (likely by purification for HSCs) in HSPCs harvests from
                      treated MM patients for subsequent ASCT might improve
                      transplant outcomes by avoiding re-infusion of cells with a
                      dysregulated and disease-linked transcriptional program.},
      keywords     = {Humans / Multiple Myeloma: therapy / Multiple Myeloma:
                      pathology / Multiple Myeloma: genetics / Hematopoietic Stem
                      Cells: metabolism / Animals / Hematopoietic Stem Cell
                      Transplantation / Mice / Female / Male / Transplantation,
                      Autologous / Antigens, CD34: metabolism / Middle Aged /
                      autologous stem cell transplantation (Other) / hematopoietic
                      stem cells (Other) / multiple myeloma (Other) / single cells
                      sequencing (Other) / xenotransplant model (Other) /
                      Antigens, CD34 (NLM Chemicals)},
      cin          = {W192},
      ddc          = {610},
      cid          = {I:(DE-He78)W192-20160331},
      pnm          = {319H - Addenda (POF4-319H)},
      pid          = {G:(DE-HGF)POF4-319H},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41259784},
      doi          = {10.1093/stcltm/szaf061},
      url          = {https://inrepo02.dkfz.de/record/306342},
}