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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},
}