ArticleNeuro-oncology2018
Modeling the diffusion of D-2-hydroxyglutarate from IDH1 mutant gliomas in the central nervous system.
Article in Neuro-oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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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.
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Who cites it
27 citing papers in PubMed.
- 7-T MRI intratumoral susceptibility signals reflect biomarker status in gliomas.European radiology experimental · 2026Article
- Treatment of Isocitrate Dehydrogenase-Mutant Gliomas.Advances in oncology · 2025Article
- The oncometabolite R-2-hydroxyglutarate inhibits microglial activation via the FTO/NF-κB pathway.Frontiers in oncology · 2025Article
- IDH mutant high-grade gliomas.Frontiers in molecular neuroscience · 2025Review
- IDH inhibition in gliomas: from preclinical models to clinical trials.Nature reviews. Neurology · 2024Review
- Glioma Response to IDH Inhibition: Real-World Experience.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- D-2-hydroxyglutarate regulates human brain vascular endothelial cell proliferation and barrier function.Journal of neuropathology and experimental neurology · 2023Article
- Postoperative risk of IDH-mutant glioma-associated seizures and their potential management with IDH-mutant inhibitors.The Journal of clinical investigation · 2023Article
- Review
- The Oncogenesis of Glial Cells in Diffuse Gliomas and Clinical Opportunities.Neuroscience bulletin · 2023Review
- D-2-Hydroxyglutarate Inhibits Calcineurin Phosphatase Activity to Abolish NF-AT Activation and IL-2 Induction in Stimulated Lymphocytes.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- New insights into the Immune TME of adult-type diffuse gliomas.Current opinion in neurology · 2022Review
- Oncometabolite d-2HG alters T cell metabolism to impair CD8Science (New York, N.Y.) · 2022Article
- The Extension of the LeiCNS-PK3.0 Model in Combination with the "Handshake" Approach to Understand Brain Tumor Pathophysiology.Pharmaceutical research · 2022Article
- Methods for intratumoral microdialysis probe targeting and validation in murine brain tumor models.Journal of neuroscience methods · 2021Article
- Contemporary Mouse Models in Glioma Research.Cells · 2021Review
- The diagnostic value of lower glucose consumption for IDH1 mutated gliomas on FDG-PET.BMC cancer · 2021Article
- Current biomarker-associated procedures of cancer modeling-a reference in the context of IDH1 mutant glioma.Cell death & disease · 2020Review
- Article
- Intratumoral Susceptibility Signals Reflect Biomarker Status in Gliomas.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Background: Among diffusely infiltrative gliomas in adults, 20%-30% contain a point mutation in isocitrate dehydrogenase 1 (IDH1mut), which increases production of D-2-hydroxyglutarate (D2HG). This is so efficient that D2HG often reaches 30 mM within IDH1mut gliomas. Yet, while up to 100 µM D2HG can be detected in the circulating cerebrospinal fluid of IDH1mut glioma patients, the exposure of nonneoplastic cells within and surrounding an IDH1mut glioma to D2HG is unknown and difficult to measure directly. Methods: Conditioned medium from patient-derived wild type IDH1 (IDH1wt) and IDH1mut glioma cells was analyzed for D2HG by liquid chromatography-mass spectrometry (LC-MS). Mathematical models of D2HG release and diffusion around an IDH1mut glioma were independently generated based on fluid dynamics within the brain and on previously reported intratumoral and cerebrospinal D2HG concentrations. Results: LC-MS analysis indicates that patient-derived IDH1mut glioma cells release 3.7-97.0 pg D2HG per cell per week. Extrapolating this to an average-sized tumor (30 mL glioma volume and 1 × 108 cells/mL tumor), the rate of D2HG release by an IDH1mut glioma (SA) is estimated at 3.2-83.0 × 10-12 mol/mL/sec. Mathematical models estimate an SA of 2.9-12.9 × 10-12 mol/mL/sec, within the range of the in vitro LC-MS data. In even the most conservative of these models, the extracellular concentration of D2HG exceeds 3 mM within a 2 cm radius from the center of an IDH1mut glioma. Conclusions: The microenvironment of an IDH1mut glioma is likely being exposed to high concentrations of D2HG, in the low millimolar range. This has implications for understanding how D2HG affects nonneoplastic cells in an IDH1mut glioma.
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