Cited by 712Acute Myeloid Leukemia ResearchCancer, Hypoxia, and MetabolismGlioma Diagnosis and Treatment

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( R )-2-Hydroxyglutarate Is Sufficient to Promote Leukemogenesis and Its Effects Are Reversible

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Losman, Julie-Aurore, Looper, Ryan E., Koivunen, Peppi, Lee, Sungwoo, Schneider, Rebekka K., McMahon, Christine, Cowley, Glenn S., Root, David E., Ebert, Benjamin L., Kaelin, William G.·2013·Science

DOI 10.1126/science.1231677PMC PMC3836459

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Abstract

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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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: Losman, Julie-Aurore
Looper, Ryan E.
Koivunen, Peppi
Schneider, Rebekka K.
McMahon, Christine
Cowley, Glenn S.
Root, David E.
Ebert, Benjamin L.
Kaelin, William G.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2013-03-29
Volume: 339
Issue: 6127
Pages: 1621-1625
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.1231677
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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( R )-2-Hydroxyglutarate Is Sufficient to Promote Leukemogenesis and Its Effects Are Reversible

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