Inhibiting glutaminase in acute myeloid leukemia: Metabolic dependency of selected AML subtypes

Oncotarget

Volumn 7, Issue 48, 2016, Pages 79722-79735

  Matre, Polina ^a   Velez, Juliana ^a   Jacamo, Rodrigo ^a   Qi, Yuan ^a   Su, Xiaoping ^a   Cai, Tianyu ^a   Chan, Steven M ^b   Lodi, Alessia ^c   Sweeney, Shannon R ^c   Ma, Helen ^a   Davis, Richard Eric ^a   Baran, Natalia ^a   Haferlach, Torsten ^d   Su, Xiaohua ^a   Flores, Elsa Renee ^a   Gonzalez, Doriann ^a   Konoplev, Sergej ^a   Samudio, Ismael ^e   DiNardo, Courtney ^a   Majeti, Ravi ^b   Schimmer, Aaron D ^f   Li, Weiqun ^g   Wang, Taotao ^g   Tiziani, Stefano ^c   Konopleva, Marina ^a   more..

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^b STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c UNIVERSITY OF TEXAS AT AUSTIN   (United States)

^d MLL MUNICH LEUKEMIA LABORATORY   (Germany)

^e Centre for Drug Research and Development   (Canada)

^f PRINCESS MARGARET HOSPITAL   (Canada)

^g Protein Analytical Chemistry   (United States)

Author keywords

Differentiation therapy; Glutamine; Leukemia; Metabolism; Microenvironment

Indexed keywords

ANTINEOPLASTIC AGENT; BIS 2 (PHENYLACETAMIDO1,2,4 THIADIAZOL 2 YL)ETHYL SULFIDE; GLUTAMATE DEHYDROGENASE; GLUTAMATE DEHYDROGENASE 1; GLUTAMINASE; GLUTAMINASE C; GLUTAMINE; HYDROLASE; ISOCITRATE DEHYDROGENASE 1; ISOCITRATE DEHYDROGENASE 2; MESSENGER RNA; UNCLASSIFIED DRUG; ALPHA-HYDROXYGLUTARATE; BENZENEACETAMIDE DERIVATIVE; BIS-2-(5-PHENYLACETAMIDO-1,2,4-THIADIAZOL-2-YL)ETHYL SULFIDE; CB-839; ENZYME INHIBITOR; GLS1 PROTEIN, HUMAN; GLUD1 PROTEIN, HUMAN; GLUTAMIC ACID; GLUTARIC ACID DERIVATIVE; IDH1 PROTEIN, HUMAN; ISOCITRATE DEHYDROGENASE; ISOCITRATE DEHYDROGENASE 2, HUMAN; ISOPROTEIN; SULFIDE; THIADIAZOLE DERIVATIVE;

ACUTE MYELOBLASTIC LEUKEMIA; ALTERNATIVE RNA SPLICING; ANTINEOPLASTIC ACTIVITY; ARTICLE; CARCINOGENESIS; CELL LEVEL; CONTROLLED STUDY; CYTOGENETICS; DISEASE ACTIVITY; DRUG EFFECT; DRUG MECHANISM; DRUG POTENCY; ENZYME INHIBITION; GENE EXPRESSION; GLUTAMATE DEHYDROGENASE 1 GENE; HUMAN; HUMAN CELL; MOLECULAR PATHOLOGY; ONCOGENE; PROTEIN EXPRESSION; ACUTE MYELOID LEUKEMIA; ANTAGONISTS AND INHIBITORS; APOPTOSIS; CELL DIFFERENTIATION; CELL PROLIFERATION; DRUG EFFECTS; ENERGY METABOLISM; ENZYMOLOGY; GENETICS; METABOLISM; MUTATION; PATHOLOGY;

ANTINEOPLASTIC AGENTS; APOPTOSIS; BENZENEACETAMIDES; CELL DIFFERENTIATION; CELL PROLIFERATION; ENERGY METABOLISM; ENZYME INHIBITORS; GLUTAMATE DEHYDROGENASE; GLUTAMIC ACID; GLUTAMINASE; GLUTAMINE; GLUTARATES; HUMANS; ISOCITRATE DEHYDROGENASE; LEUKEMIA, MYELOID, ACUTE; MUTATION; PROTEIN ISOFORMS; SULFIDES; THIADIAZOLES;

EID: 84998881905     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.12944     Document Type: Article

References (43)

1. Wise DR, DeBerardinis RJ, Mancuso A, Sayed N, Zhang XY, Pfeiffer HK, Nissim I, Daikhin E, Yudkoff M, McMahon SB, Thompson CB. Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction. Proc Natl Acad Sci U S A. 2008; 10548:18782-18787.
2. Wang JB, Erickson JW, Fuji R, Ramachandran S, Gao P, Dinavahi R, Wilson KF, Ambrosio AL, Dias SM, Dang CV, Cerione RA. Targeting mitochondrial glutaminase activity inhibits oncogenic transformation. Cancer Cell. 2010; 183:207-219.
3. Gross MI, Demo SD, Dennison JB, Chen L, Chernov-Rogan T, Goyal B, Janes JR, Laidig GJ, Lewis ER, Li J, Mackinnon AL, Parlati F, Rodriguez ML, Shwonek PJ, Sjogren EB, Stanton TF, Wang T, Yang J, Zhao F, Bennett MK. Antitumor activity of the glutaminase inhibitor CB-839 in triple-negative breast cancer. Mol Cancer Ther. 2014; 134:890-901.
4. Robinson MM, McBryant SJ, Tsukamoto T, Rojas C, Ferraris DV, Hamilton SK, Hansen JC, Curthoys NP. Novel mechanism of inhibition of rat kidney-type glutaminase by bis-2-(5-phenylacetamido-1, 2, 4-thiadiazol-2-yl)ethyl sulfide (BPTES). The Biochemical journal. 2007; 4063:407-414.
5. DeLaBarre B, Gross S, Fang C, Gao Y, Jha A, Jiang F, Song JJ, Wei W, Hurov JB. Full-length human glutaminase in complex with an allosteric inhibitor. Biochemistry. 2011; 5050:10764-10770.
6. Hartwick EW, Curthoys NP. BPTES inhibition of hGA(124-551), a truncated form of human kidney-type glutaminase. Journal of enzyme inhibition and medicinal chemistry. 2012; 276:861-867.
7. Jacque N, Ronchetti AM, Larrue C, Meunier G, Birsen R, Willems L, Saland E, Decroocq J, Maciel TT, Lambert M, Poulain L, Hospital MA, Sujobert P, Joseph L, Chapuis N, Lacombe C, Moura IC, Demo S, Sarry JE, Recher C, Mayeux P, Tamburini J, Bouscary D. Targeting glutaminolysis has antileukemic activity in acute myeloid leukemia and synergizes with BCL-2 inhibition. Blood. 2015; 12611:1346-1356.
8. Willems L, Jacque N, Jacquel A, Neveux N, Maciel TT, Lambert M, Schmitt A, Poulain L, Green AS, Uzunov M, Kosmider O, Radford-Weiss I, Moura IC, Auberger P, Ifrah N, Bardet V, Chapuis N, Lacombe C, Mayeux P, Tamburini J, Bouscary D. Inhibiting glutamine uptake represents an attractive new strategy for treating acute myeloid leukemia. Blood. 2013; 12220:3521-3532.
9. Goto M, Miwa H, Shikami M, Tsunekawa-Imai N, Suganuma K, Mizuno S, Takahashi M, Mizutani M, Hanamura I, Nitta M. Importance of glutamine metabolism in leukemia cells by energy production through TCA cycle and by redox homeostasis. Cancer Invest. 2014; 326:241-247.
10. Seltzer MJ, Bennett BD, Joshi AD, Gao P, Thomas AG, Ferraris DV, Tsukamoto T, Rojas CJ, Slusher BS, Rabinowitz JD, Dang CV, Riggins GJ. Inhibition of glutaminase preferentially slows growth of glioma cells with mutant IDH1. Cancer Res. 2010; 7022:8981-8987.
11. Dang L, White DW, Gross S, Bennett BD, Bittinger MA, Driggers EM, Fantin VR, Jang HG, Jin S, Keenan MC, Marks KM, Prins RM, Ward PS, Yen KE, Liau LM, Rabinowitz JD, Cantley LC, Thompson CB, Vander Heiden MG, Su SM. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature. 2010; 4657300:966.
12. Emadi A, Jun SA, Tsukamoto T, Fathi AT, Minden MD, Dang CV. Inhibition of glutaminase selectively suppresses the growth of primary acute myeloid leukemia cells with IDH mutations. Exp Hematol. 2014; 424:247-251.
13. Haferlach T, Kohlmann A, Wieczorek L, Basso G, Kronnie GT, Bene MC, De Vos J, Hernandez JM, Hofmann WK, Mills KI, Gilkes A, Chiaretti S, Shurtleff SA, Kipps TJ, Rassenti LZ, Yeoh AE, Papenhausen PR, Liu WM, Williams PM, Foa R. Clinical utility of microarray-based gene expression profiling in the diagnosis and subclassification of leukemia: report from the International Microarray Innovations in Leukemia Study Group. J Clin Oncol. 2010; 2815:2529-2537.
14. Verhaak RG, Wouters BJ, Erpelinck CA, Abbas S, Beverloo HB, Lugthart S, Lowenberg B, Delwel R, Valk PJ. Prediction of molecular subtypes in acute myeloid leukemia based on gene expression profiling. Haematologica. 2009; 941:131-134.
15. Wouters BJ, Jorda MA, Keeshan K, Louwers I, Erpelinck-Verschueren CA, Tielemans D, Langerak AW, He Y, Yashiro-Ohtani Y, Zhang P, Hetherington CJ, Verhaak RG, Valk PJ, Lowenberg B, Tenen DG, Pear WS, Delwel R. Distinct gene expression profiles of acute myeloid/T-lymphoid leukemia with silenced CEBPA and mutations in NOTCH1. Blood. 2007; 11010:3706-3714.
16. Chan SM, Thomas D, Corces-Zimmerman MR, Xavy S, Rastogi S, Hong WJ, Zhao F, Medeiros BC, Tyvoll DA, Majeti R. Isocitrate dehydrogenase 1 and 2 mutations induce BCL-2 dependence in acute myeloid leukemia. Nat Med. 2015; 212:178-184.
17. Samudio I, Fiegl M, McQueen T, Clise-Dwyer K, Andreeff M. The warburg effect in leukemia-stroma cocultures is mediated by mitochondrial uncoupling associated with uncoupling protein 2 activation. Cancer Res. 2008; 6813:5198-5205.
18. Le A, Lane AN, Hamaker M, Bose S, Gouw A, Barbi J, Tsukamoto T, Rojas CJ, Slusher BS, Zhang H, Zimmerman LJ, Liebler DC, Slebos RJ, Lorkiewicz PK, Higashi RM, Fan TW, Dang CV. Glucose-independent glutamine metabolism via TCA cycling for proliferation and survival in B cells. Cell Metab. 2012; 151:110-121.
19. Cheng T, Sudderth J, Yang C, Mullen AR, Jin ES, Mates JM, DeBerardinis RJ. Pyruvate carboxylase is required for glutamine-independent growth of tumor cells. Proc Natl Acad Sci U S A. 2011; 10821:8674-8679.
20. Samudio I, Harmancey R, Fiegl M, Kantarjian H, Konopleva M, Korchin B, Kaluarachchi K, Bornmann W, Duvvuri S, Taegtmeyer H, Andreeff M. Pharmacologic inhibition of fatty acid oxidation sensitizes human leukemia cells to apoptosis induction. J Clin Invest. 2010; 1201:142-156.
21. Lagadinou ED, Sach A, Callahan K, Rossi RM, Neering SJ, Minhajuddin M, Ashton JM, Pei S, Grose V, O'Dwyer KM, Liesveld JL, Brookes PS, Becker MW, Jordan CT. BCL-2 inhibition targets oxidative phosphorylation and selectively eradicates quiescent human leukemia stem cells. Cell Stem Cell. 2013; 123:329-341.
22. Xu W, Yang H, Liu Y, Yang Y, Wang P, Kim SH, Ito S, Yang C, Wang P, Xiao MT, Liu LX, Jiang WQ, Liu J, Zhang JY, Wang B, Frye S, Zhang Y, Xu YH, Lei QY, Guan KL, Zhao SM, Xiong Y. Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of alpha-ketoglutarate-dependent dioxygenases. Cancer Cell. 2011; 191:17-30.
23. Iyer LM, Tahiliani M, Rao A, Aravind L. Prediction of novel families of enzymes involved in oxidative and other complex modifications of bases in nucleic acids. Cell Cycle. 2009; 811:1698-1710.
24. Hausinger RP. FeII/alpha-ketoglutarate-dependent hydroxylases and related enzymes. Critical reviews in biochemistry and molecular biology. 2004; 391:21-68.
25. Loenarz C, Schofield CJ. Expanding chemical biology of 2-oxoglutarate oxygenases. Nature chemical biology. 2008; 43:152-156.
26. Rose NR, McDonough MA, King ON, Kawamura A, Schofield CJ. Inhibition of 2-oxoglutarate dependent oxygenases. Chemical Society reviews. 2011; 408:4364-4397.
27. Kernytsky A, Wang F, Hansen E, Schalm S, Straley K, Gliser C, Yang H, Travins J, Murray S, Dorsch M, Agresta S, Schenkein DP, Biller SA, Su SM, Liu W, Yen KE. IDH2 mutation-induced histone and DNA hypermethylation is progressively reversed by small-molecule inhibition. Blood. 2015; 1252:296-303.
28. Wang F, Travins J, DeLaBarre B, Penard-Lacronique V, Schalm S, Hansen E, Straley K, Kernytsky A, Liu W, Gliser C, Yang H, Gross S, Artin E, Saada V, Mylonas E, Quivoron C, Popovici-Muller J, Saunders JO, Salituro FG, Yan S, Murray S, Wei W, Gao Y, Dang L, Dorsch M, Agresta S, Schenkein DP, Biller SA, Su SM, de Botton S, Yen KE. Targeted inhibition of mutant IDH2 in leukemia cells induces cellular differentiation. Science. 2013; 3406132:622-626.
29. Dinardo C, Stein E, Altman J, Collins R, DeAngelo D, Fathi A, Flinn I, Frankel AE, Levine R, Medeiros B, Patel M, Pollyea D, Roboz G. (2015). AG-221, an oral, selective, first-in-class, potent inhibitor of the IDH2 mutant enzyme, induced durable responses in a phase 1 study of IDH2 mutation-positive advanced hematologic malignancies. Annual Meeting of the European Hematology Association, pp. E947.
30. Konopleva M, Flinn IW, Wang ES, Dinardo CD, Bennett MK, Molineaux CJ, Le MH, Maris MB, Frankfurt O. (2015). Phase 1 Study: Safety and tolerability of increasing doses of CB-839, an orally-administered small molecule inhibitor of glutaminase, in acute leukemia. Annual Meeting of the European Hematology Association, pp. P569.
31. Ricciardi MR, Mirabilii S, Allegretti M, Licchetta R, Calarco A, Torrisi MR, Foa R, Nicolai R, Peluso G, Tafuri A. Targeting the leukemia cell metabolism by the CPT1a inhibition: functional preclinical effects in leukemias. Blood. 2015; 12616:1925-1929.
32. Zhang W, Trachootham D, Liu J, Chen G, Pelicano H, Garcia-Prieto C, Lu W, Burger JA, Croce CM, Plunkett W, Keating MJ, Huang P. Stromal control of cystine metabolism promotes cancer cell survival in chronic lymphocytic leukaemia. Nature cell biology. 2012; 143:276-286.
33. Li J, Chen L, Goyal B, Laidig GJ, Stanton TF, Sjogren EB. (2013). Heterocyclic inhibitors of glutaminase. (United States: Calithera Biosciences).
34. Jacamo R, Chen Y, Wang Z, Ma W, Zhang M, Spaeth EL, Wang Y, Battula VL, Mak PY, Schallmoser K, Ruvolo P, Schober WD, Shpall EJ, Nguyen MH, Strunk D, Bueso-Ramos CE, Konoplev S, Davis RE, Konopleva M, Andreeff M. Reciprocal leukemia-stroma VCAM-1/VLA-4-dependent activation of NF-kappaB mediates chemoresistance. Blood. 2014; 12317:2691-2702.
35. Battula VL, Chen Y, Cabreira Mda G, Ruvolo V, Wang Z, Ma W, Konoplev S, Shpall E, Lyons K, Strunk D, Bueso-Ramos C, Davis RE, Konopleva M, Andreeff M. Connective tissue growth factor regulates adipocyte differentiation of mesenchymal stromal cells and facilitates leukemia bone marrow engraftment. Blood. 2013; 1223:357-366.
36. Ma W, Wang M, Wang ZQ, Sun L, Graber D, Matthews J, Champlin R, Yi Q, Orlowski RZ, Kwak LW, Weber DM, Thomas SK, Shah J, Kornblau S, Davis RE. Effect of long-term storage in TRIzol on microarray-based gene expression profiling. Cancer Epidemiol Biomarkers Prev. 2010; 1910:2445-2452.
37. A J, Trygg J, Gullberg J, Johansson AI, Jonsson P, Antti H, Marklund SL, Moritz T. Extraction and GC/MS analysis of the human blood plasma metabolome. Anal Chem. 2005; 7724:8086-8094.
38. Fan TW, Lane AN, Higashi RM, Farag MA, Gao H, Bousamra M, Miller DM. Altered regulation of metabolic pathways in human lung cancer discerned by 13 C stable isotope-resolved metabolomics (SIRM). Molecular cancer. 2009; 81:1.
39. Guma M, Tiziani S, Firestein GS. Metabolomics in rheumatic diseases: desperately seeking biomarkers. Nature Reviews Rheumatology. 2016.
40. Lodi A, Tiziani S, Khanim FL, Drayson MT, Guenther UL, Bunce CM, Viant MR. Hypoxia Triggers Major Metabolic Changes in AML Cells without Altering Indomethacin-Induced TCA Cycle Deregulation. Acs Chemical Biology. 2011; 62:169-175.
41. Tiziani S, Lodi A, Khanim FL, Viant MR, Bunce CM, Guenther UL. Metabolomic Profiling of Drug Responses in Acute Myeloid Leukaemia Cell Lines. Plos One. 2009; 41.
42. Robinson MD, Oshlack A. A scaling normalization method for differential expression analysis of RNA-seq data. Genome biology. 2010; 113:R25.
43. Robinson MD, McCarthy DJ, Smyth GK. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 2010; 261:139-140.