ArticleJCI insight2018
Glutamine-derived 2-hydroxyglutarate is associated with disease progression in plasma cell malignancies.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05539079 (A Prospective Long-term Observational Study in Patients With Monoclonal Gammopathy of Undetermined Significance), which is not on this map. Cited by 39 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.
A Prospective Long-term Observational Study in Patients With Monoclonal Gammopathy of Undetermined Significance
Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Can Targeting Hypoxia-Mediated Acidification of the Bone Marrow Microenvironment Kill Myeloma Tumor Cells?Frontiers in oncology · 2021Pooled it
- Glutamine metabolism in health and disease.Signal transduction and targeted therapy · 2026Review
- 3D biomimetic microgel platform for multiple myeloma: Approaching tumor microenvironment on cell lines and patient-derived cells.Materials today. Bio · 2026Article
- A metabolic trade-off between malignant plasma cells and mesenchymal stromal cells sustains multiple myeloma growth.Blood neoplasia · 2026Article
- 2-Hydroxyglutarate in onco-pathway: a metabolic driver of proto-oncogene activation.Frontiers in oncology · 2026Review
- Lactate metabolism in clonal plasma cells and its therapeutic implications in multiple myeloma patients with elevated serum LDH levels.Cancer & metabolism · 2025Article
- Targeting Caveolin-1 in Multiple Myeloma Cells Enhances Chemotherapy and Natural Killer Cell-Mediated Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Review
- Glutamine addiction in tumor cell: oncogene regulation and clinical treatment.Cell communication and signaling : CCS · 2024Review
- Lipid metabolic vulnerabilities of multiple myeloma.Clinical and experimental medicine · 2023Review
- Mitochondrial dysfunction and drug targets in multiple myeloma.Journal of cancer research and clinical oncology · 2023Review
- Noncanonical role of singleminded-2s in mitochondrial respiratory chain formation in breast cancer.Experimental & molecular medicine · 2023Article
- Metabolic Alterations in Multiple Myeloma: From Oncogenesis to Proteasome Inhibitor Resistance.Cancers · 2023Review
- Metabolic changes underlying drug resistance in the multiple myeloma tumor microenvironment.Frontiers in oncology · 2023Article
- Shutting off the fuel supply to target metabolic vulnerabilities in multiple myeloma.Frontiers in oncology · 2023Review
- In good times and in bad: How plasma cells resolve stress for a life-long union with the bone marrow.Frontiers in immunology · 2023Article
- Article
- Overexpression of the energy metabolism transcriptome within clonal plasma cells is associated with the pathogenesis and outcomes of patients with multiple myeloma.American journal of hematology · 2022Article
- Multiple myeloma metabolism - a treasure trove of therapeutic targets?Frontiers in immunology · 2022Review
- Contribution of the Tumor Microenvironment to Metabolic Changes Triggering Resistance of Multiple Myeloma to Proteasome Inhibitors.Frontiers in oncology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
The production of the oncometabolite 2-hydroxyglutarate (2-HG) has been associated with c-MYC overexpression. c-MYC also regulates glutamine metabolism and drives progression of asymptomatic precursor plasma cell (PC) malignancies to symptomatic multiple myeloma (MM). However, the presence of 2-HG and its clinical significance in PC malignancies is unknown. By performing 13C stable isotope resolved metabolomics (SIRM) using U[13C6]Glucose and U[13C5]Glutamine in human myeloma cell lines (HMCLs), we show that 2-HG is produced in clonal PCs and is derived predominantly from glutamine anaplerosis into the TCA cycle. Furthermore, the 13C SIRM studies in HMCLs also demonstrate that glutamine is preferentially utilized by the TCA cycle compared with glucose. Finally, measuring the levels of 2-HG in the BM supernatant and peripheral blood plasma from patients with precursor PC malignancies such as smoldering MM (SMM) demonstrates that relatively elevated levels of 2-HG are associated with higher levels of c-MYC expression in the BM clonal PCs and with a subsequent shorter time to progression (TTP) to MM. Thus, measuring 2-HG levels in BM supernatant or peripheral blood plasma of SMM patients offers potential early identification of those patients at high risk of progression to MM, who could benefit from early therapeutic intervention.
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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.