| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Ghamlouch, Hussein Gagler, Dylan C. Blaney, Patrick Boyle, Eileen M. Wang, Yubao Avigan, Jason Choi, Jinyoung Landgren, Ola Tsirigos, Aristotelis Maura, Francesco Morgan, Gareth J. Davies, Faith E. |
| Abstract | Background The bone marrow (BM) niche contains non-hematopoietic elements including mesenchymal stromal cells (MSC) and bone marrow endothelial cells (BMEC) which provide mechanical support, and control hematopoietic cell growth and differentiation. Although it is known that multiple myeloma (MM) cells interact closely with the BM microenvironment, little is known about the impact of MM on non-hematopoietic niche-forming cells. Methods To address the role of the niche in MM pathogenesis, we utilized the 5TGM1 murine model. During the asymptomatic precursor stage of the model, we isolated the rare non-hematopoietic cells and performed single cell RNA sequencing. Using in-silico methods we characterized the individual cellular components of the niche, their relative abundance and differentiation state before and after exposure to MM cells as well as their intercellular interactions. Results MM engraftment increased the abundance of MSC-lineage cells, BMECs and enhanced endothelial to mesenchymal transition. An inflammatory and oxidative stress signal was identified together with polarization of MSC differentiation away from osteocyte formation towards adipocytes which provide growth factors that are known to support MM expansion. BMEC differentiation was polarized towards sinusoidal endothelial cells with a pro-angiogenic/pro-inflammatory phenotype. Conclusions MM cells impact the BM niche by generating a pro-inflammatory microenvironment with MSC differentiation being changed to generate cell subsets that favor MM growth and survival. In order to induce remission and improve long-term outcome for MM patients these inflammatory and oxidative stress signals need to be reduced and normal niche differentiation trajectories restored. |
| Related Links | https://ehoonline.biomedcentral.com/counter/pdf/10.1186/s40164-025-00606-x.pdf |
| Ending Page | 14 |
| Page Count | 14 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 21623619 |
| DOI | 10.1186/s40164-025-00606-x |
| Journal | Experimental Hematology & Oncology |
| Issue Number | 1 |
| Volume Number | 14 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2025-02-26 |
| Access Restriction | Open |
| Subject Keyword | Hematology Oncology Cancer Research Myeloma Niche Pro-inflammatory response Bone marrow stress Polarized differentiation Mesenchymal stromal cells Microenvironment EndoMT |
| Content Type | Text |
| Resource Type | Article |
| Subject | Hematology Oncology Cancer Research |
| Journal Impact Factor | 9.4/2023 |
| 5-Year Journal Impact Factor | 8.3/2023 |
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