A small molecule inhibitor of mutant IDH2 rescues cardiomyopathy in a D-2-hydroxyglutaric aciduria type II mouse model

Journal of Inherited Metabolic Disease

Volumn 39, Issue 6, 2016, Pages 807-820

  Wang, Fang ^a   Travins, Jeremy ^a   Lin, Zhizhong ^b   Si, Yaguang ^a   Chen, Yue ^a   Powe, Josh ^a   Murray, Stuart ^a   Zhu, Dongwei ^a   Artin, Erin ^a   Gross, Stefan ^a   Santiago, Stephanie ^a   Steadman, Mya ^a   Kernytsky, Andrew ^a   Straley, Kimberly ^a   Lu, Chenming ^b   Pop, Ana ^c   Struys, Eduard A ^c   Jansen, Erwin E W ^c   Salomons, Gajja S ^c   David, Muriel D ^d,e   Quivoron, Cyril ^d,e   Penard Lacronique, Virginie ^d,e   Regan, Karen S ^f   Liu, Wei ^a   Dang, Lenny ^a   Yang, Hua ^a   Silverman, Lee ^a   Agresta, Samuel ^a   Dorsch, Marion ^a   Biller, Scott ^a   Yen, Katharine ^a   Cang, Yong ^b   Su, Shin San Michael ^a   Jin, Shengfang ^a   more..

^a AGIOS PHARMACEUTICALS   (United States)

^b WUXI APPTEC   (China)

^c VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^d INSERM   (France)

^e INSTITUT GUSTAVE ROUSSY   (France)

^f Regan Pathology/Toxicology Services   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 HYDROXYGLUTARIC ACID; AGI 026; ENZYME INHIBITOR; ISOCITRATE DEHYDROGENASE 2; UNCLASSIFIED DRUG; ISOCITRATE DEHYDROGENASE; ISOCITRATE DEHYDROGENASE 2, MOUSE;

ACIDURIA; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CARDIOMYOPATHY; CONTROLLED STUDY; DEVELOPMENTAL DISORDER; DEXTRO 2 HYDROXYGLUTARIC ACIDURIA TYPE II; DRUG POTENCY; ECHOCARDIOGRAPHY; EMBRYO; ENZYME ACTIVITY; ENZYME INHIBITION; EPILEPSY; EXPRESSION VECTOR; FEMALE; GENETIC ENGINEERING; IC50; MALE; MOUSE; MOUSE EMBRYONIC STEM CELL; NONHUMAN; RNA SEQUENCE; TREATMENT WITHDRAWAL; ANIMAL; ANTAGONISTS AND INHIBITORS; DISEASE MODEL; DRUG EFFECTS; GENETICS; METABOLIC ENCEPHALOPATHY; MOLECULAR LIBRARY; MUTATION; PHARMACOLOGY;

ANIMALS; BRAIN DISEASES, METABOLIC, INBORN; CARDIOMYOPATHIES; DISEASE MODELS, ANIMAL; ISOCITRATE DEHYDROGENASE; MICE; MUTATION; SMALL MOLECULE LIBRARIES;

EID: 84980018969     PISSN: 01418955     EISSN: 15732665     Source Type: Journal    
DOI: 10.1007/s10545-016-9960-y     Document Type: Article

References (59)

1. Akbay EA, Moslehi J, Christensen CL et al (2014) D-2-hydroxyglutarate produced by mutant IDH2 causes cardiomyopathy and neurodegeneration in mice. Genes Dev 28:479–490
2. Allard MF, Schonekess BO, Henning SL, English DR, Lopaschuk GD (1994) Contribution of oxidative metabolism and glycolysis to ATP production in hypertrophied hearts. Am J Physiol 267:H742–H750
3. Buescher JM, Moco S, Sauer U, Zamboni N (2010) Ultrahigh performance liquid chromatography-tandem mass spectrometry method for fast and robust quantification of anionic and aromatic metabolites. Anal Chem 82:4403–4412
4. Chen L, Liu H, Friedman C (2005) Gene name ambiguity of eukaryotic nomenclatures. Bioinformatics 21:248–256
5. Chen C, Liu Y, Lu C et al (2013) Cancer-associated IDH2 mutants drive an acute myeloid leukemia that is susceptible to Brd4 inhibition. Genes Dev 27:1974–1985
6. Chowdhury R, Yeoh KK, Tian YM et al (2011) The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases. EMBO Rep 12:463–469
7. Christiansen LB, Dela F, Koch J, Hansen CN, Leifsson PS, Yokota T (2015) Impaired cardiac mitochondrial oxidative phosphorylation and enhanced mitochondrial oxidative stress in feline hypertrophic cardiomyopathy. Am J Physiol Heart Circ Physiol 308:H1237–H1247
8. Dang L, White DW, Gross S et al (2009) Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 462:739–744
9. Delgado-Olguin P, Huang Y, Li X et al (2012) Epigenetic repression of cardiac progenitor gene expression by Ezh2 is required for postnatal cardiac homeostasis. Nat Genet 44:343–347
10. Dennis G Jr, Sherman BT, Hosack DA et al (2003) DAVID: database for annotation, visualization, and integrated discovery. Genome Biol 4:P3
11. Depre C, Ponchaut S, Deprez J, Maisin L, Hue L (1998) Cyclic AMP suppresses the inhibition of glycolysis by alternative oxidizable substrates in the heart. J Clin Invest 101:390–397
12. Faupel RP, Seitz HJ, Tarnowski W, Thiemann V, Weiss C (1972) The problem of tissue sampling from experimental animals with respect to freezing technique, anoxia, stress and narcosis. A new method for sampling rat liver tissue and the physiological values of glycolytic intermediates and related compounds. Arch Biochem Biophys 148:509–522
13. Figueroa ME, Abdel-Wahab O, Lu C et al (2010) Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell 18:553–567
14. Friedman C, Kra P, Yu H, Krauthammer M, Rzhetsky A (2001) GENIES: a natural-language processing system for the extraction of molecular pathways from journal articles. Bioinformatics 17(Suppl 1):S74–S82
15. Gross S, Cairns RA, Minden MD et al (2010) Cancer-associated metabolite 2-hydroxyglutarate accumulates in acute myelogenous leukemia with isocitrate dehydrogenase 1 and 2 mutations. J Exp Med 207:339–344
16. Hale R (2005) Text mining: getting more value from literature resources. Drug Discov Today 10:377–379
17. Harvey PA, Leinwand LA (2011) The cell biology of disease: cellular mechanisms of cardiomyopathy. J Cell Biol 194:355–365
18. Hearse DJ (1983) Myocardial cyclic AMP determinations: the importance of rapidity of sample freezing. J Mol Cell Cardiol 15:653–657
19. Huang DW, Sherman BT, Lempicki RA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4:44–57
20. Ingwall JS (2009) Energy metabolism in heart failure and remodelling. Cardiovasc Res 81:412–419
21. Ito S, Shen L, Dai Q et al (2011) Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science 333:1300–1303
22. Jensen LJ, Saric J, Bork P (2006) Literature mining for the biologist: from information retrieval to biological discovery. Nat Rev Genet 7:119–129
23. Jha AK, Huang SC, Sergushichev A et al (2015) Network integration of parallel metabolic and transcriptional data reveals metabolic modules that regulate macrophage polarization. Immunity 42:419–430
24. Kernytsky A, Wang F, Hansen E et al (2015) IDH2 mutation-induced histone and DNA hypermethylation is progressively reversed by small-molecule inhibition. Blood 125:296–303
25. Kim D, Pertea G, Trapnell C, Pimentel H, Kelley R, Salzberg SL (2013) TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol 14:R36
26. Kranendijk M, Struys EA, Gibson KM et al (2010a) Evidence for genetic heterogeneity in D-2-hydroxyglutaric aciduria. Hum Mutat 31:279–283
27. Kranendijk M, Struys EA, van Schaftingen E et al (2010b) IDH2 mutations in patients with D-2-hydroxyglutaric aciduria. Science 330:336
28. Kranendijk M, Struys EA, Salomons GS, Van der Knaap MS, Jakobs C (2012) Progress in understanding 2-hydroxyglutaric acidurias. J Inherit Metab Dis 35:571–587
29. Kraus TF, Globisch D, Wagner M et al (2012) Low values of 5-hydroxymethylcytosine (5hmC), the “sixth base,” are associated with anaplasia in human brain tumors. Int J Cancer 131:1577–1590
30. Kroeze LI, Aslanyan MG, van Rooij A et al (2014) Characterization of acute myeloid leukemia based on levels of global hydroxymethylation. Blood 124:1110–1118
31. Lee EC, Yu D, Martinez de Velasco J et al (2001) A highly efficient Escherichia coli-based chromosome engineering system adapted for recombinogenic targeting and subcloning of BAC DNA. Genomics 73:56–65
32. Li J, Mayne R, Wu C (1999) A novel muscle-specific beta 1 integrin binding protein (MIBP) that modulates myogenic differentiation. J Cell Biol 147:1391–1398
33. Liu Y, Jiang W, Liu J et al (2012) IDH1 mutations inhibit multiple alpha-ketoglutarate-dependent dioxygenase activities in astroglioma. J Neurooncol 109:253–260
34. Lu C, Ward PS, Kapoor GS et al (2012) IDH mutation impairs histone demethylation and results in a block to cell differentiation. Nature 483:474–478
35. Mardis ER, Ding L, Dooling DJ et al (2009) Recurring mutations found by sequencing an acute myeloid leukemia genome. N Engl J Med 361:1058–1066
36. Maurice DH, Palmer D, Tilley DG et al (2003) Cyclic nucleotide phosphodiesterase activity, expression, and targeting in cells of the cardiovascular system. Mol Pharmacol 64:533–546
37. Movassagh M, Choy MK, Knowles DA et al (2011) Distinct epigenomic features in end-stage failing human hearts. Circulation 124:2411–2422
38. Movsesian MA (2004) Altered cAMP-mediated signalling and its role in the pathogenesis of dilated cardiomyopathy. Cardiovasc Res 62:450–459
39. Mylonas E, Janin M, Bawa O et al (2014) Isocitrate dehydrogenase (IDH)2 R140Q mutation induces myeloid and lymphoid neoplasms in mice. Leukemia 28:1343–1346
40. Novichkova S, Egorov S, Daraselia N (2003) MedScan, a natural language processing engine for MEDLINE abstracts. Bioinformatics 19:1699–1706
41. Reitman ZJ, Jin G, Karoly ED et al (2011) Profiling the effects of isocitrate dehydrogenase 1 and 2 mutations on the cellular metabolome. Proc Natl Acad Sci U S A 108:3270–3275
42. Ruggieri S, Orsomando G, Sorci L, Raffaelli N (2015) Regulation of NAD biosynthetic enzymes modulates NAD-sensing processes to shape mammalian cell physiology under varying biological cues. Biochim Biophys Acta 1854:1138–1149
43. Stein EM, Altman JK, Collins R et al (2014) AG-221, an oral, selective, first-in-class, potent inhibitor of the IDH2 mutant metabolic enzyme, induces durable remissions in a phase I study in patients with IDH2 mutation positive advanced hematologic malignancies. Blood 124(21):Abstract 115
44. Strauss AW, Johnson MC (1996) The genetic basis of pediatric cardiovascular disease. Semin Perinatol 20:564–576
45. Struys EA, Jansen EE, Verhoeven NM, Jakobs C (2004) 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 50:1391–1395
46. Struys EA, Salomons GS, Achouri Y et al (2005) Mutations in the D-2-hydroxyglutarate dehydrogenase gene cause D-2-hydroxyglutaric aciduria. Am J Hum Genet 76:358–360
47. Trapnell C, Pachter L, Salzberg SL (2009) TopHat: discovering splice junctions with RNA-Seq. Bioinformatics 25:1105–1111
48. Trapnell C, Williams BA, Pertea G et al (2010) Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat Biotechnol 28:511–515
49. Trapnell C, Hendrickson DG, Sauvageau M, Goff L, Rinn JL, Pachter L (2013) Differential analysis of gene regulation at transcript resolution with RNA-seq. Nat Biotechnol 31:46–53
50. Trivedi CM, Cappola TP, Margulies KB, Epstein JA (2011) Homeodomain only protein x is down-regulated in human heart failure. J Mol Cell Cardiol 50:1056–1058
51. Turcan S, Rohle D, Goenka A et al (2012) IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype. Nature 483:479–483
52. Ussher JR, Jaswal JS, Lopaschuk GD (2012) Pyridine nucleotide regulation of cardiac intermediary metabolism. Circ Res 111:628–641
53. Wang F, Travins J, DeLaBarre B et al (2013a) Targeted inhibition of mutant IDH2 in leukemia cells induces cellular differentiation. Science 340:622–626
54. Wang P, Dong Q, Zhang C et al (2013b) Mutations in isocitrate dehydrogenase 1 and 2 occur frequently in intrahepatic cholangiocarcinomas and share hypermethylation targets with glioblastomas. Oncogene 32:3091–3100
55. Wickenhagen WV, Salomons GS, Gibson KM, Jakobs C, Struys EA (2009) Measurement of D-2-hydroxyglutarate dehydrogenase activity in cell homogenates derived from D-2-hydroxyglutaric aciduria patients. J Inherit Metab Dis 32:264–268
56. Wu W, Huang R, Wu Q et al (2014) The role of Six1 in the genesis of muscle cell and skeletal muscle development. Int J Biol Sci 10:983–989
57. Xu W, Yang H, Liu Y et al (2011) Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of alpha-ketoglutarate-dependent dioxygenases. Cancer Cell 19:17–30
58. Yan H, Parsons DW, Jin G et al (2009) IDH1 and IDH2 mutations in gliomas. N Engl J Med 360:765–773
59. Zhao X, Huang Z, Liu X et al (2013) The switch role of the Tmod4 in the regulation of balanced development between myogenesis and adipogenesis. Gene 532:263–271