Imprinting of Mesenchymal Stromal Cell Transcriptome Persists even after Treatment in Patients with Multiple Myeloma
Open accessAbstract
Introduction. Multiple myeloma (MM) is a B-cell neoplasm characterized by clonal expansion of malignant plasma cells (MM cells) in the bone-marrow (BM) compartment. BM mesenchymal stromal cells (MSC) from newly diagnosed MM patients were shown to be involved in MM pathogenesis and chemoresistance. The patients displayed a distinct transcriptome and were functionally different from healthy donors’ (HD) MSC. Our aim was to determine whether MM–MSC also contributed to relapse. Methods. We obtained and characterized patients’ MSC samples at diagnosis, two years after intensive treatment, without relapse and at relapse. Results. Transcriptomic analysis revealed differences in gene expression between HD and MM-MSC, whatever the stage of the disease. An easier differentiation towards adipogenesis at the expense of osteoblatogeneis was observed, even in patients displaying a complete response to treatment. Although their transcriptome was similar, we found that MSC from relapsed patients had an increased immunosuppressive ability, compared to those from patients in remission. Conclusion. We demonstrated that imprinting of MSC transcriptome demonstrated at diagnosis of MM, persisted even after the apparent disappearance of MM cells induced by treatment, suggesting the maintenance of a local context favorable to relapse.
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Changes possibly brought about by epigenetic reprogramming caused by the presence of multiple myeloma plasma cells in the bone marrow cause mesenchymal stromal cells to change into a persistent pro-tumoral phenotype.
“Ultimately, they discovered that changes, possibly brought about by epigenetic reprogramming, caused by the presence of MM PC in the BM caused the MSC to change into a persistent pro-tumoral phenotype.”
From Mesenchymal stromal cells in bone marrow niche of patients with multiple myeloma: a double-edged sword (2025) · cites this paper as [284]
Mesenchymal stromal cells can contribute to the recurrence of multiple myeloma by encouraging the development of minimal residual cells.
“Furthermore, they proposed that MSC can contribute to the recurrence of MM by encouraging the development of minimal residual cells [284].”
From Mesenchymal stromal cells in bone marrow niche of patients with multiple myeloma: a double-edged sword (2025) · cites this paper as [284]
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Self-citation
- Authors
- Lemaitre, L., Do Souto Ferreira, L., Joubert, M.-V., Avet-Loiseau, H., Martinet, L., Corre, J., & Couderc, B.
- Affiliations
- UMR 1037 INSERM, 31059 Toulouse, France
- Inserm (FR)
- Université Toulouse III - Paul Sabatier (FR)
- Corresponding author
- Corre, Jill
- Couderc, Bettina
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2020-05-28
- Volume
- 21
- Issue
- 11
- Pages
- 3854
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC7312921
- OpenAlex
- W3032585289
- Cited by
- 13
- References
- 42
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 5 · 2022: 1 · 2021: 1 · 2020: 1
- FWCI
- 1.33
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Institut Claudius Regaud
- Topics
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- multiple myeloma, mesenchymal stem cells, recurrence, bone marrow microenvironment, immunosuppression, adipogenesis, osteogenic differentiation, chemoresistance, treatment response
- MeSH terms
- Aged, Bone Marrow, Bone Marrow Cells, Cell Differentiation, Female, Humans, Immunosuppressive Agents, Leukocytes, Mononuclear, Male, Middle Aged, Multiple Myeloma, Neoplasm Recurrence, Local, Recurrence, T-Lymphocytes, Gene Expression Regulation, Neoplastic, Genomic Imprinting, Coculture Techniques, Drug Resistance, Neoplasm, Gene Expression Profiling, Principal Component Analysis, Adipogenesis, Transcriptome, Mesenchymal Stem Cells
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