ArticleCancers2020
Myeloma Cells Deplete Bone Marrow Glutamine and Inhibit Osteoblast Differentiation Limiting Asparagine Availability.
Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 39 citations in OpenAlex.
- N-Acetylornithine Depletion in Bone Marrow Biopsy: A Novel Microenvironment-Specific Hallmark for Multiple Myeloma Diagnosis.International journal of laboratory hematology · 2026Article
- A metabolic trade-off between malignant plasma cells and mesenchymal stromal cells sustains multiple myeloma growth.Blood neoplasia · 2026Article
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- Article
- The Gut Microbiome Role in Multiple Myeloma: Emerging Insights and Therapeutic Opportunities.Hematology reports · 2025Review
- Article
- PI3K Signaling Pathway Inhibitor Affects Myeloma Cells in a Culture-Dependent Manner.Advanced pharmaceutical bulletin · 2025Article
- Construction of a treatment response prediction model for multiple myeloma based on multi-omics and machine learning.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Article
- Mechanistic insights into bone destruction in multiple myeloma: Cellular and molecular perspectives.Journal of bone oncology · 2025Review
- Mesenchymal stromal cells in bone marrow niche of patients with multiple myeloma: a double-edged sword.Cancer cell international · 2025Review
- Identification ofHaematologica · 2024Article
- Engagement of Mesenchymal Stromal Cells in the Remodeling of the Bone Marrow Microenvironment in Hematological Cancers.Biomolecules · 2023Review
- Amino Acid Metabolism in Bone Metastatic Disease.Current osteoporosis reports · 2023Review
- Metabolic crosstalk between stromal and malignant cells in the bone marrow niche.Bone reports · 2023Article
- The Interaction between Gut Microbiota and Host Amino Acids Metabolism in Multiple Myeloma.Cancers · 2023Review
- The Metabolic Features of Osteoblasts: Implications for Multiple Myeloma (MM) Bone Disease.International journal of molecular sciences · 2023Review
- Metabolic changes underlying drug resistance in the multiple myeloma tumor microenvironment.Frontiers in oncology · 2023Article
- Cuproptosis-a potential target for the treatment of osteoporosis.Frontiers in endocrinology · 2023Review
- Amino acid metabolism in skeletal cells.Bone reports · 2022Article
- Metabolic cross-talk within the bone marrow milieu: focus on multiple myeloma.Experimental hematology & oncology · 2022Review
Corrections and comments
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Authors and funding
24 authors at 5 institutions in 2 countries.
Funding
Abstract
Multiple myeloma (MM) cells consume huge amounts of glutamine and, as a consequence, the amino acid concentration is lower-than-normal in the bone marrow (BM) of MM patients. Here we show that MM-dependent glutamine depletion induces glutamine synthetase in stromal cells, as demonstrated in BM biopsies of MM patients, and reproduced in vitro by co-culturing human mesenchymal stromal cells (MSCs) with MM cells. Moreover, glutamine depletion hinders osteoblast differentiation of MSCs, which is also severely blunted by the spent, low-glutamine medium of MM cells, and rescued by glutamine restitution. Glutaminase and the concentrative glutamine transporter SNAT2 are induced during osteoblastogenesis in vivo and in vitro, and both needed for MSCs differentiation, pointing to enhanced the requirement for the amino acid. Osteoblastogenesis also triggers the induction of glutamine-dependent asparagine synthetase (ASNS), and, among non-essential amino acids, asparagine rescues differentiation of glutamine-starved MSCs, by restoring the transcriptional profiles of differentiating MSCs altered by glutamine starvation. Thus, reduced asparagine availability provides a mechanistic link between MM-dependent Gln depletion in BM and impairment of osteoblast differentiation. Inhibition of Gln metabolism in MM cells and supplementation of asparagine to stromal cells may, therefore, constitute novel approaches to prevent osteolytic lesions in MM.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.