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Differential distribution of CCDC26 glioma-risk alleles in myeloid malignancies with mutant IDH1 compared with their IDH2R140-mutated or IDH-unmutated counterparts

Leukemia volume 26, pages 1406–1407 (2012)Cite this article

Isocitrate dehydrogenase-1 and isocitrate dehydrogenase-2 (IDH1 and IDH2) encode enzymes that convert isocitrate to α-ketoglutarate (α-KG). IDH mutations are common in some cancers and currently known IDH mutations affect three specific arginine residues: R132 (IDH1), R172 (IDH2) and R140 (IDH2). The R172 of IDH1 is homologous to the R132 of IDH2: both are located at the active catalytic sites of the enzymes. IDH1 and IDH2 mutations result in reduced synthesis of α-KG and an acquired ability to convert α-KG to 2-hydroxyglutarate. The latter is believed to be a competitive inhibitor of α-KG-dependent enzymes, including histone demethylases and the Ten-Eleven Translocation family of 5-methlycytosine hydroxylases, thus leading to altered histone and DNA methylation.1

IDH1R132 and IDH2R172 mutations are most prevalent in low-grade gliomas and secondary glioblastomas (mutational frequency ∼70% and ∼5%, respectively), but not IDH2R140 mutations.2, 3 In contrast, mutations affecting all three IDH arginine residues have been described in myeloid malignancies, including acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), myeloproliferative neoplasm (MPN) and MDS/MPN.4 In general, IDH mutational frequencies in myeloid neoplasms are substantially lower than those seen in low-grade gliomas. In both AML and chronic myeloid neoplasms, the incidences of IDH2R140 (5–10%) and IDH1R132 (5–10%) mutations are similar, but IDH2R172 mutations are less frequent.5, 6, 7

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Authors and Affiliations

  1. Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA

    T L Lasho, A Tefferi, A Pardanani & C M Finke

  2. Division of Cytogenetics, Department of Laboratory Medicine, Mayo Clinic, Rochester, MN, USA

    S R Fink, A A Caron & R B Jenkins

  3. Department of Laboratory Medicine and Pathology, Division of Health Sciences Research, Mayo Clinic, Rochester, MN, USA

    P A Decker

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Lasho, T., Tefferi, A., Pardanani, A. et al. Differential distribution of CCDC26 glioma-risk alleles in myeloid malignancies with mutant IDH1 compared with their IDH2R140-mutated or IDH-unmutated counterparts. Leukemia 26, 1406–1407 (2012). https://doi.org/10.1038/leu.2011.336

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