The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
( R )-2-Hydroxyglutarate Is Sufficient to Promote Leukemogenesis and Its Effects Are Reversible
Open accessAbstract
Focusing on the Right Metabolite: A variety of human cancers, including acute leukemias and brain tumors, have mutations in the genes encoding isocitrate dehydrogenase 1 or 2 (IDH1, IDH2), which cause overproduction of a metabolite called 2-hydroxyglutarate (2HG). Losman et al. (p. 1621 , published online 7 February) show that the R - but not the S -enantiomer of 2HG can transform cells and that R -2HG mediates transformation at least in part through effects on protein modifying EglN prolyl hydroxylases. Importantly, the transforming activity of R -2HG was reversible, suggesting that therapeutic strategies focusing on inhibition of R -2HG production or inhibition of EglN prolyl hydroxylases merit further investigation.
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“A high level of R-2-HG is sufficient to cause leukemia to arise from hematopoietic cells by maintaining their dedifferentiation and proliferation activities116.”
From Glutamine reliance in cell metabolism (2020) · cites this paper as [116]
In the citing paper
“Interestingly, R-2HG is sufficient to promote cytokine independence and block differentiation of hematopoietic cells in vitro and these effects are fairly rapidly reversed upon R-2HG withdrawal (Losman et al., 2013; K. Yen, personal communication).”
From Influence of Metabolism on Epigenetics and Disease (2013) · cites this paper as Losman et al., 2013
In the citing paper
“In various cellular settings, ectopic expression of a mutant IDH allele or treatment with exogenous D-2-HG is sufficient to induce DNA and histone hypermethylation and block cellular differentiation (Losman et al., 2013; Lu et al., 2012).”
From The emerging hallmarks of cancer metabolism (2016) · cites this paper as Losman et al., 2013
In the citing paper
“all suggesting that cellular reprogramming elicited by D-2-HG may play a prominent role in the pathogenesis of IDH-mutant tumours135-137.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [135]
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Cites
Targeting Hypoxia-Inducible Factors for the Treatment of Anemia in Chronic Kidney Disease Patients
Locatelli, F., Fishbane, S. N., Block, G. A., & Macdougall, I. C. (2017) · American Journal of Nephrology · doi:10.1159/000455166 · Cited by 4,836
Cancer-associated IDH1 mutations produce 2-hydroxyglutarate
Dang, L., White, D. W., Gross, S., Bennett, B. D., Bittinger, M. A., Driggers, E. M., Fantin, V. R., Jang, H. G., Jin, S., Keenan, M. C., et al. (2009) · Nature · doi:10.1038/nature08617 · Cited by 4,154
Xu, W., Yang, H., Liu, Y., Yang, Y., Wang, P., Kim, S.-H., Ito, S., Yang, C., Wang, P., Xiao, M.-T., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2010.12.014 · Cited by 2,875
Figueroa, M. E., Abdel-Wahab, O., Lu, C., Ward, P. S., Patel, J., Shih, A., Li, Y., Bhagwat, N., Vasanthakumar, A., Fernandez, H. F., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.11.015 · Cited by 2,766
Recurring mutations found by sequencing an acute myeloid leukemia genome
Mardis, E. R., Ding, L., Dooling, D. J., Larson, D. E., McLellan, M. D., Chen, K., Koboldt, D. C., Fulton, R. S., Delehaunty, K. D., McGrath, S. D., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0903840 · Cited by 2,219
Ward, P. S., Patel, J., Wise, D. R., Abdel-Wahab, O., Bennett, B. D., Coller, H. A., Cross, J. R., Fantin, V. R., Hedvat, C. V., Perl, A. E., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.01.020 · Cited by 2,020
Mutation in TET2 in Myeloid Cancers
Delhommeau, F., Dupont, S., Valle, V. D., James, C., Trannoy, S., Massé, A., Kosmider, O., Le Couedic, J.-P., Robert, F., Alberdi, A., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0810069 · Cited by 1,776
Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation
Moran-Crusio, K., Reavie, L., Shih, A., Abdel-Wahab, O., Ndiaye-Lobry, D., Lobry, C., Figueroa, M. E., Vasanthakumar, A., Patel, J., Zhao, X., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.06.001 · Cited by 1,339
The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases
Chowdhury, R., Yeoh, K. K., Tian, Y., Hillringhaus, L., Bagg, E. A., Rose, N. R., Leung, I. K. H., Li, X. S., Woon, E. C. Y., Yang, M., et al. (2011) · The EMBO Reports · doi:10.1038/embor.2011.43 · Cited by 1,035
Regulation of the HIF-1α Level Is Essential for Hematopoietic Stem Cells
Takubo, K., Goda, N., Yamada, W., Iriuchishima, H., Ikeda, E., Kubota, Y., Shima, H., Johnson, R. S., Hirao, A., Suematsu, M., et al. (2010) · Cell Stem Cell · doi:10.1016/j.stem.2010.06.020 · Cited by 891
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Kopinski, P. K., Magi, I. J., & Dalvin, L. A. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-19001-8.00026-x
BindingDB (2019) · UC San Diego · doi:10.7270/q2bc41z0
BindingDB Entry 50013577: Discovery and Optimization of 2
BindingDB (2022) · UC San Diego · doi:10.7270/q2ff3x3s
BindingDB Entry 7446: New IDH1 mutant inhibitors for treatment of acute myeloid leukemia
BindingDB (2016) · UC San Diego · doi:10.7270/q2rr1x2g
Metabolic Adaptation in Reprogrammed Cancer Cells
Marks, K. M., & Kung, C. K.-H. (2014) · Cancer drug discovery and develogment/Cancer drug discovery and development · doi:10.1007/978-1-4614-9545-1_7
Metadata
- Authors
- Losman, J.-A., Looper, R. E., Koivunen, P., Lee, S., Schneider, R. K., McMahon, C., Cowley, G. S., Root, D. E., Ebert, B. L., & Kaelin, W. G.
- Affiliations
- Brigham and Women's Hospital (US)
- University of Utah (US)
- University of Oulu (FI)
- Dana-Farber Cancer Institute (US)
- Broad Institute (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Kaelin, William G.
- ORCID
- Venue
- Science
- Published
- 2013-03-29
- Volume
- 339
- Issue
- 6127
- Pages
- 1621-1625
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC3836459
- OpenAlex
- W2012588998
- Cited by
- 703
- References
- 32
- Citations by year
- 2026: 17 · 2025: 23 · 2024: 43 · 2023: 31 · 2022: 50 · 2021: 70 · 2020: 49 · 2019: 43 · 2018: 68 · 2017: 60 · 2016: 67 · 2015: 56 · 2014: 63 · 2013: 62
- FWCI
- 59.57
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Cancer Institute (R01CA068490)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK049216)
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Oncology › Glioma Diagnosis and Treatment
- Keywords
- (R)-2-hydroxyglutarate, leukemogenesis, IDH1 R132H mutation, IDH2 mutation, isocitrate dehydrogenase, enantiomers, TET2, hematopoietic differentiation, reversible transformation, cancer cell models
- MeSH terms
- Cell Transformation, Neoplastic, Glutarates, Hematopoiesis, Humans, Isocitrate Dehydrogenase, Leukemia, Models, Biological, Procollagen-Proline Dioxygenase, Cell Line, Tumor
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