ArticleHaematologica2024
A NOTCH3-CXCL12-driven myeloma-tumor niche signaling axis promotes chemoresistance in multiple myeloma.
Article in Haematologica, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 10 citations in OpenAlex.
- Drug Resistance in Multiple Myeloma: Tumor-Intrinsic Mechanisms and the Bone Marrow Microenvironment.Cell biochemistry and function · 2026Review
- SSTNSignal transduction and targeted therapy · 2026Article
- An enhancement of extrachromosomal circular DNA enrichment and amplification to address the extremely low overlap between replicates.The Journal of biological chemistry · 2026Article
- Targeting NOTCH3 to eradicate dormant and therapy-resistant multiple myeloma cells.Journal of experimental & clinical cancer research : CR · 2026Article
- Myeloid-derived suppressor cells in multiple myeloma: mechanistic insights and therapeutic implications.Frontiers in immunology · 2026Review
- Carnosic acid alleviates 5-Fluorouracil chemoresistance and enhances CD8Frontiers in immunology · 2026Article
- Age-dependent effects of chronic traumatic and social isolation stress on mice social behavior.Neurobiology of stress · 2026Article
- Human preclinical multiple myeloma in vitro models for disease modeling and therapy screening.Journal of biological engineering · 2025Review
- Healing of lytic lesions and restoration of bone health in multiple myeloma through sclerostin inhibition.Experimental hematology & oncology · 2025Article
- A novel CCL3-HMGB1 signaling axis regulating osteocyte RANKL expression in multiple myeloma.Haematologica · 2025Article
- 2D and 3D In Vitro Co-culture for Cancer and Bone Cell Interaction Studies.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Single-Cell Transcriptomic Analysis Identifies Senescent Osteocytes That Trigger Bone Destruction in Breast Cancer Metastasis.Cancer research · 2024Article
- 2D and 3D In Vitro Co-Culture for Cancer and Bone Cell Interaction Studies.Methods in molecular biology (Clifton, N.J.) · 2019Article
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Multiple myeloma (MM) remains incurable due to disease relapse and drug resistance. Notch signals from the tumor microenvironment (TME) confer chemoresistance, but the cellular and molecular mechanisms are not entirely understood. Using clinical and transcriptomic datasets, we found that NOTCH3 is upregulated in CD138+ cells from newly diagnosed MM (NDMM) patients compared to healthy individuals and increased in progression/relapsed MM (PRMM) patients. Further, NDMM patients with high NOTCH3 expression exhibited worse responses to bortezomib (BOR)-based therapies. Cells of the TME, including osteocytes, upregulated NOTCH3 in MM cells and protected them from apoptosis induced by BOR. NOTCH3 activation (NOTCH3OE) in MM cells decreased BOR anti-MM efficacy and its ability to improve survival in in vivo myeloma models. Molecular analyses revealed that NDMM and PRMM patients with high NOTCH3 exhibit CXCL12 upregulation. TME cells upregulated CXCL12 and activated the CXCR4 pathway in MM cells in a NOTCH3-dependent manner. Moreover, genetic or pharmacologic inhibition of CXCL12 in NOTCH3OE MM cells restored sensitivity to BOR regimes in vitro and in human bones bearing NOTCH3OE MM tumors cultured ex vivo. Our clinical and preclinical data unravel a novel NOTCH3-CXCL12 pro-survival signaling axis in the TME and suggest that osteocytes transmit chemoresistance signals to MM cells.
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