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Updated: Feb 13, 2026

Primary Orthotopic Glioma Xenografts Recapitulate Infiltrative Growth and Isocitrate Dehydrogenase I Mutation
Published on: January 14, 2014
Isocitrate dehydrogenase 2 mutations correlate with leukemic transformation and are predicted by 2-hydroxyglutarate
Peipei Lin1,2,3, Yingwan Luo1,2,3, Shuanghong Zhu1,2,3
1Department of Hematology, The First Affiliated Hospital, Zhejiang University, No. 79 Qingchun Road, Hangzhou, 310003, People's Republic of China.
Purpose:
The myelodysplastic syndromes (MDS) are a group of hematologic disorders characterized by the presence of somatically mutated hematopoietic stem cells (HSCs) that increase the risk of progression to secondary acute myeloid leukemia (sAML). Mutations in isocitrate dehydrogenase (IDHmut) are thought to correlate with the increased production of the oncogenic protein 2-hydroxyglutarate (2-HG) in AML. The aim of this study was to examine whether serum 2-HG has utility as a prognostic biomarker, and whether elevated 2-HG levels are predictive of IDH mutations in patients with MDS.
Methods:
Genetic profiling was utilized to determine the genetic composition of a large cohort of MDS patients, including the presence or absence of IDH1 or IDH2 mutations (n = 281). Serum 2-HG levels were detected by liquid chromatography-tandem mass spectrometry.
Results:
In the current study of MDS patients, elevated serum 2-HG levels were predictive of inferior overall- and leukemia-free survival irrespective of IPSS risk grouping. Higher serum 2-HG levels predicted the presence of IDH mutations. IDH2mut patients had a higher risk of leukemic transformation. The co-occurrence of DNMT3A or SRSF2 mutations was found to be increased in IDH2mut patients. IDH2 mutations were associated with significantly worse OS and LFS amongst patients with low-risk MDS by IPSS grouping.
Conclusions:
The noted predictive value of serum 2-HG levels and IDH2 mutations on OS and LFS support the use of biomarkers and/or underlying cytogenetics in novel prognostic scoring systems for MDS.
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