- Mardis ER, Ding L, Dooling DJ, Larson DE, McLellan MD, Chen K et al. Recurring mutations found by sequencing an acute myeloid leukemia genome. N Engl J Med 2009; 361: 1058–1066.
Article CAS Google Scholar
- Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W et al. IDH1 and IDH2 mutations in gliomas. N Engl J Med 2009; 360: 765–773.
Article CAS Google Scholar
- Amary MF, Bacsi K, Maggiani F, Damato S, Halai D, Berisha F et al. IDH1 and IDH2 mutations are frequent events in central chondrosarcoma and central and periosteal chondromas but not in other mesenchymal tumours. J Pathol 2011; 224: 334–343.
Article CAS Google Scholar
- Borger DR, Tanabe KK, Fan KC, Lopez HU, Fantin VR, Straley KS et al. Frequent mutation of isocitrate dehydrogenase (IDH)1 and IDH2 in cholangiocarcinoma identified through broad-based tumor genotyping. Oncologist 2012; 17: 72–79.
Article CAS Google Scholar
- Thol F, Damm F, Wagner K, Gohring G, Schlegelberger B, Hoelzer D et al. Prognostic impact of IDH2 mutations in cytogenetically normal acute myeloid leukemia. Blood 2010; 116: 614–616.
Article CAS Google Scholar
- Wagner K, Damm F, Gohring G, Gorlich K, Heuser M, Schafer I et al. Impact of IDH1 R132 mutations and an IDH1 single nucleotide polymorphism in cytogenetically normal acute myeloid leukemia: SNP rs11554137 is an adverse prognostic factor. J Clin Oncol 2010; 28: 2356–2364.
Article CAS Google Scholar
- Paschka P, Schlenk RF, Gaidzik VI, Habdank M, Kronke J, Bullinger L et al. IDH1 and IDH2 mutations are frequent genetic alterations in acute myeloid leukemia and confer adverse prognosis in cytogenetically normal acute myeloid leukemia with NPM1 mutation without FLT3 internal tandem duplication. J Clin Oncol 2010; 28: 3636–3643.
Article CAS Google Scholar
- Ward PS, Patel J, Wise DR, Abdel-Wahab O, Bennett BD, Coller HA et al. The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate. Cancer Cell 2010; 17: 225–234.
Article CAS Google Scholar
- Dang L, White DW, Gross S, Bennett BD, Bittinger MA, Driggers EM et al. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 2010; 465: 966.
Article CAS Google Scholar
- Gross S, Cairns RA, Minden MD, Driggers EM, Bittinger MA, Jang HG et al. Cancer-associated metabolite 2-hydroxyglutarate accumulates in acute myelogenous leukemia with isocitrate dehydrogenase 1 and 2 mutations. J Exp Med 2010; 207: 339–344.
Article CAS Google Scholar
- Zhao S, Lin Y, Xu W, Jiang W, Zha Z, Wang P et al. Glioma-derived mutations in IDH1 dominantly inhibit IDH1 catalytic activity and induce HIF-1alpha. Science 2009; 324: 261–265.
Article CAS Google Scholar
- Rose NR, McDonough MA, King ON, Kawamura A, Schofield CJ . Inhibition of 2-oxoglutarate dependent oxygenases. Chem Soc Rev 2011; 40: 4364–4397.
Article CAS Google Scholar
- Loenarz C, Schofield CJ . Expanding chemical biology of 2-oxoglutarate oxygenases. Nat Chem Biol 2008; 4: 152–156.
Article CAS Google Scholar
- Xu W, Yang H, Liu Y, Yang Y, Wang P, Kim SH et al. Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of alpha-ketoglutarate-dependent dioxygenases. Cancer Cell 2011; 19: 17–30.
Article CAS Google Scholar
- Chowdhury R, Yeoh KK, Tian YM, Hillringhaus L, Bagg EA, Rose NR et al. The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases. EMBO Rep 2011; 12: 463–469.
Article CAS Google Scholar
- Koivunen P, Lee S, Duncan CG, Lopez G, Lu G, Ramkissoon S et al. Transformation by the (_R_-enantiomer of 2-hydroxyglutarate linked to EGLN activation. Nature 2012; 483: 484–488.
Article CAS Google Scholar
- Heuser M, Araujo Cruz MM, Goparaju R, Chaturvedi A . Enigmas of IDH mutations in hematology/oncology. Exp Hematol 2015; 43: 685–697.
Article CAS Google Scholar
- Sasaki M, Knobbe CB, Munger JC, Lind EF, Brenner D, Brustle A et al. IDH1(R132H) mutation increases murine haematopoietic progenitors and alters epigenetics. Nature 2012; 488: 656–659.
Article CAS Google Scholar
- Chaturvedi A, Araujo Cruz MM, Jyotsana N, Sharma A, Yun H, Gorlich K et al. Mutant IDH1 promotes leukemogenesis in vivo and can be specifically targeted in human AML. Blood 2013; 122: 2877–2887.
Article CAS Google Scholar
- Heuser M, Yun H, Berg T, Yung E, Argiropolous B, Kuchenbauer F et al. Cell of origin in AML: Susceptibility to MN1-induced transformation is regulated by the MEIS1/AbdB-like HOX protein complex. Cancer Cell 2011; 20: 39–52.
Article CAS Google Scholar
- Heuser M, Sly LM, Argiropoulos B, Kuchenbauer F, Lai C, Weng A et al. Modeling the functional heterogeneity of leukemia stem cells: role of STAT5 in leukemia stem cell self-renewal. Blood 2009; 114: 3983–3993.
Article CAS Google Scholar
- Struys EA, Jansen EE, Verhoeven NM, Jakobs C . Measurement of urinary d- and l-2-hydroxyglutarate enantiomers by stable-isotope-dilution liquid chromatography-tandem mass spectrometry after derivatization with diacetyl-l-tartaric anhydride. Clin Chem 2004; 50: 1391–1395.
Article CAS Google Scholar
- Gentleman RC, Carey VJ, Bates DM, Bolstad B, Dettling M, Dudoit S et al. Bioconductor: open software development for computational biology and bioinformatics. Genome Biol 2004; 5: R80.
Article Google Scholar
- Kauffmann A, Gentleman R, Huber W . arrayQualityMetrics—a bioconductor package for quality assessment of microarray data. Bioinformatics 2009; 25: 415–416.
Article CAS Google Scholar
- Gautier L, Cope L, Bolstad BM, Irizarry RA . affy—analysis of Affymetrix GeneChip data at the probe level. Bioinformatics 2004; 20: 307–315.
Article CAS Google Scholar
- Smyth GK . LIMMA: Linear Models for Microarray Data Bioinformatics and Computational Biology Solutions Using R and Bioconductor, Part V. Springer: New York, NY, USA,, 2005, Mpp 397–420.
Book Google Scholar
- Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA 2005; 102: 15545–15550.
Article CAS Google Scholar
- Heuser M, Beutel G, Krauter J, Dohner K, von Neuhoff N, Schlegelberger B et al. High meningioma 1 (MN1) expression as a predictor for poor outcome in acute myeloid leukemia with normal cytogenetics. Blood 2006; 108: 3898–3905.
Article CAS Google Scholar
- Heuser M, Yap DB, Leung M, de Algara TR, Tafech A, McKinney S et al. Loss of MLL5 results in pleiotropic hematopoietic defects, reduced neutrophil immune function, and extreme sensitivity to DNA demethylation. Blood 2009; 113: 1432–1443.
Article CAS Google Scholar
- Livak KJ, Schmittgen TD . Analysis of relative gene expression data using real-time quantitative PCR and the 2(−delta delta C(T)) method. Methods 2001; 25: 402–408.
Article CAS Google Scholar
- Smith ZD, Gu H, Bock C, Gnirke A, Meissner A . High-throughput bisulfite sequencing in mammalian genomes. Methods 2009; 48: 226–232.
Article CAS Google Scholar
- Xi Y, Li W . BSMAP: whole genome bisulfite sequence MAPping program. BMC Bioinform 2009; 10: 232.
Article Google Scholar
- Lister R, Pelizzola M, Dowen RH, Hawkins RD, Hon G, Tonti-Filippini J et al. Human DNA methylomes at base resolution show widespread epigenomic differences. Nature 2009; 462: 315–322.
Article CAS Google Scholar
- Lu C, Ward PS, Kapoor GS, Rohle D, Turcan S, Abdel-Wahab O et al. IDH mutation impairs histone demethylation and results in a block to cell differentiation. Nature 2012; 483: 474–478.
Article CAS Google Scholar
- Losman JA, Looper RE, Koivunen P, Lee S, Schneider RK, McMahon C et al. (_R_-2-hydroxyglutarate is sufficient to promote leukemogenesis and its effects are reversible. Science 2013; 339: 1621–1625.
Article CAS Google Scholar
- Chan SM, Thomas D, Corces-Zimmerman MR, Xavy S, Rastogi S, Hong WJ et al. Isocitrate dehydrogenase 1 and 2 mutations induce BCL-2 dependence in acute myeloid leukemia. Nat Med 2015; 21: 178–184.
Article CAS Google Scholar
- Kats LM, Reschke M, Taulli R, Pozdnyakova O, Burgess K, Bhargava P et al. Proto-oncogenic role of mutant IDH2 in leukemia initiation and maintenance. Cell Stem Cell 2014; 14: 329–341.
Article CAS Google Scholar
- Kranendijk M, Struys EA, Salomons GS, Van der Knaap MS, Jakobs C . Progress in understanding 2-hydroxyglutaric acidurias. J Inherit Metab Dis 2012; 35: 571–587.
Article CAS Google Scholar