ArticleBlood advances2021
ALL blasts drive primary mesenchymal stromal cells to increase asparagine availability during asparaginase treatment.
Article in Blood advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- A metabolic trade-off between malignant plasma cells and mesenchymal stromal cells sustains multiple myeloma growth.Blood neoplasia · 2026Article
- Metabolic reprogramming in tumor-associated cells of hematologic malignancies: mechanisms, crosstalk networks, and therapeutic implications in the tumor microenvironment.Frontiers in immunology · 2026Review
- Suppression of ASNS expression by VHL-mediated ubiquitination hinders the progression of renal cell carcinoma through enhancing JUP expression and inhibiting PI3K-AKT and MAPK pathways.International journal of biological sciences · 2026Article
- Mesenchymal Stromal Cells: Bridging the Gaps in Hematologic Disease Therapy.Stem cell reviews and reports · 2026Review
- Integrated metabolomic and transcriptomic analysis identifies adipogenic differentiation of mesenchymal stem cells as a driver of chemoresistance in acute myeloid leukemia.Journal of experimental & clinical cancer research : CR · 2025Article
- Targeting asparagine potentiates anti-PD-L1 immunotherapy in gastric cancer by enhancing CD8Frontiers in immunology · 2025Article
- Molecular and cellular mechanisms of chemoresistance in paediatric pre-B cell acute lymphoblastic leukaemia.Cancer metastasis reviews · 2024Review
- Emerging roles for stromal cells in bone metastasis.Journal of bone oncology · 2024Article
- Biology and Therapeutic Properties of Mesenchymal Stem Cells in Leukemia.International journal of molecular sciences · 2024Review
- Metabolic crosstalk between stromal and malignant cells in the bone marrow niche.Bone reports · 2023Article
- Mesenchymal stromal cells, metabolism, and mitochondrial transfer in bone marrow normal and malignant hematopoiesis.Frontiers in cell and developmental biology · 2023Review
- Mesenchymal stroma/stem cells: Haematologists' friend or foe?British journal of haematology · 2022Review
- Review
- The TLR4/NFκB-Dependent Inflammatory Response Activated by LPS Is Inhibited in Human Macrophages Pre-Exposed to Amorphous Silica Nanoparticles.Nanomaterials (Basel, Switzerland) · 2022Article
- Bone Marrow Aging and the Leukaemia-Induced Senescence of Mesenchymal Stem/Stromal Cells: Exploring Similarities.Journal of personalized medicine · 2022Review
- Physiological Media in Studies of Cell Metabolism.Molecular biology · 2022Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
Abstract
Mechanisms underlying the resistance of acute lymphoblastic leukemia (ALL) blasts to l-asparaginase are still incompletely known. Here we demonstrate that human primary bone marrow mesenchymal stromal cells (MSCs) successfully adapt to l-asparaginase and markedly protect leukemic blasts from the enzyme-dependent cytotoxicity through an amino acid trade-off. ALL blasts synthesize and secrete glutamine, thus increasing extracellular glutamine availability for stromal cells. In turn, MSCs use glutamine, either synthesized through glutamine synthetase (GS) or imported, to produce asparagine, which is then extruded to sustain asparagine-auxotroph leukemic cells. GS inhibition prevents mesenchymal cells adaptation to l-asparaginase, lowers glutamine secretion by ALL blasts, and markedly hinders the protection exerted by MSCs on leukemic cells. The pro-survival amino acid exchange is hindered by the inhibition or silencing of the asparagine efflux transporter SNAT5, which is induced in mesenchymal cells by ALL blasts. Consistently, primary MSCs from ALL patients express higher levels of SNAT5 (P < .05), secrete more asparagine (P < .05), and protect leukemic blasts (P < .05) better than MSCs isolated from healthy donors. In conclusion, ALL blasts arrange a pro-leukemic amino acid trade-off with bone marrow mesenchymal cells, which depends on GS and SNAT5 and promotes leukemic cell survival during l-asparaginase treatment.
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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.