Journal Article

DKFZ-2025-02558

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Functional and molecular analyses reveal impaired HSPCs in Multiple Myeloma patients post-induction.

Baumhardt, T. M. ; Amoah, A. ; Hoenicka, M. ; Liebold, A. ; Sakk, V. ; Soller, K. ; Vollmer, A. ; Kull, M. ; Kronke, J. ; Mallm, J.-P.DKFZ* ; Geiger, H. ; Mulaw, M.

2025
Oxford University Press Oxford

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.

Keyword(s): Humans (MeSH) ; Multiple Myeloma: therapy (MeSH) ; Multiple Myeloma: pathology (MeSH) ; Multiple Myeloma: genetics (MeSH) ; Hematopoietic Stem Cells: metabolism (MeSH) ; Animals (MeSH) ; Hematopoietic Stem Cell Transplantation (MeSH) ; Mice (MeSH) ; Female (MeSH) ; Male (MeSH) ; Transplantation, Autologous (MeSH) ; Antigens, CD34: metabolism (MeSH) ; Middle Aged (MeSH) ; autologous stem cell transplantation ; hematopoietic stem cells ; multiple myeloma ; single cells sequencing ; xenotransplant model ; Antigens, CD34

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Contributing Institute(s):

1. Single-cell Open Lab (W192)

Research Program(s):

1. 311 - Zellbiologie und Tumorbiologie (POF4-311) (POF4-311)

Appears in the scientific report 2025

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Database coverage:
; ; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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