ArticleThe Journal of clinical investigation2007
Mesenchymal cells regulate the response of acute lymphoblastic leukemia cells to asparaginase.
Article in The Journal of clinical investigation, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 161 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
161 citing papers in PubMed, 1 synthesis or guideline pooled it, 332 citations in OpenAlex.
- Genome-wide association analyses for meat quality traits in Chinese Erhualian pigs and a Western Duroc × (Landrace × Yorkshire) commercial population.Genetics, selection, evolution : GSE · 2015Pooled it
- Trial
- CXCR4 chemokine receptor signaling induces apoptosis in acute myeloid leukemia cells via regulation of the Bcl-2 family members Bcl-XL, Noxa, and Bak.The Journal of biological chemistry · 2013Trial
- Comparison of native E. coli and PEG asparaginase pharmacokinetics and pharmacodynamics in pediatric acute lymphoblastic leukemia.Clinical pharmacology and therapeutics · 2009Trial
- Trial
- Central nervous system involvement in acute lymphoblastic leukemia: pathogenesis and targeted therapy.Leukemia · 2026Review
- From ALL to Myeloid and NK Malignancies: Operationalizing "ASNS-Low" for L-Asparaginase Repurposing and Combination Therapy.Biomolecules · 2026Review
- Tumor metabolic adaptation induced by L-asparaginase reveals a vulnerability to PARP1/2 inhibitor in B-cell lymphomas.Nature communications · 2026Article
- An Integrated Method to Evaluate the Treatment Efficacy and Immunogenicity of B-Cell Acute Lymphoblastic Leukemia Therapeutic Enzyme Formulations.Small methods · 2026Article
- FGF2-regulated Osteogenic Differentiation of Human Bone Marrow Stromal Cells.Current stem cell research & therapy · 2026Article
- Antileukemia efficacy of the dual BCL2/BCL-XL inhibitor AZD0466 in acute lymphoblastic leukemia preclinical models.Blood advances · 2025Article
- Molecular and cellular mechanisms of chemoresistance in paediatric pre-B cell acute lymphoblastic leukaemia.Cancer metastasis reviews · 2024Review
- Article
- Metabolism of asparagine in the physiological state and cancer.Cell communication and signaling : CCS · 2024Review
- Utility ofEpigenetics · 2023Article
- Skin mesenchymal niches maintain and protect AML-initiating stem cells.The Journal of experimental medicine · 2023Article
- Tumor microenvironmental nutrients, cellular responses, and cancer.Cell chemical biology · 2023Review
- Discovery and Targeting of a Noncanonical Mechanism of Sarcoma Resistance to ADI-PEG20 Mediated by the Microenvironment.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Stromal-induced epithelial-mesenchymal transition induces targetable drug resistance in acute lymphoblastic leukemia.Cell reports · 2023Article
- Metabolic crosstalk between stromal and malignant cells in the bone marrow niche.Bone reports · 2023Article
101 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Because of their low asparagine synthetase (ASNS) expression and asparagine biosynthesis, acute lymphoblastic leukemia (ALL) cells are exquisitely sensitive to asparagine depletion. Consequently, asparaginase is a major component of ALL therapy, but the mechanisms regulating the susceptibility of leukemic cells to this agent are unclear. In 288 children with ALL, cellular ASNS expression was more likely to be high in T-lineage ALL and low in B-lineage ALL with TEL-AML1 or hyperdiploidy. However, ASNS expression levels in bone marrow-derived mesenchymal cells (MSCs), which form the microenvironment where leukemic cells grow, were on average 20 times higher than those in ALL cells. MSCs protected ALL cells from asparaginase cytotoxicity in coculture experiments. This protective effect correlated with levels of ASNS expression: downregulation by RNA interference decreased the capacity of MSCs to protect ALL cells from asparaginase, whereas enforced ASNS expression conferred enhanced protection. Asparagine secretion by MSCs was directly related to their ASNS expression levels, suggesting a mechanism - increased concentrations of asparagine in the leukemic cell microenvironment - for the protective effects we observed. These results provide what we believe to be a new basis for understanding asparaginase resistance in ALL and indicate that MSC niches in the bone marrow can form a safe haven for leukemic cells.
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What OpenQuestion holds
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.