AMPK-ULK1-mediated autophagy confers resistance to BET inhibitor JQ1 in acute myeloid leukemia stem cells

Clinical Cancer Research

Volumn 23, Issue 11, 2017, Pages 2781-2794

  Jang, Ji Eun ^a   Eom, Ju In ^b   Jeung, Hoi Kyung ^b   Cheong, June Won ^a   Lee, Jung Yeon ^a   Kim, Jin Seok ^a   Min, Yoo Hong ^a  

^a Yonsei University College of Medicine   (South Korea)

^b Yonsei University College of Medicine   (South Korea)

Author keywords

[No Author keywords available]

Indexed keywords

4 (4 CHLOROPHENYL) 2,3,9 TRIMETHYL 6H THIENO[3,2 F][1,2,4]TRIAZOLO[4,3 A][1,4]DIAZEPINE 6 ACETIC ACID TERT BUTYL ESTER; BECLIN 1; CASPASE 3; CASPASE 9; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; MAMMALIAN TARGET OF RAPAMYCIN; MICROTUBULE ASSOCIATED PROTEIN 1; MYC PROTEIN; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE; SEQUESTOSOME 1; SERINE THREONINE PROTEIN KINASE ULK1; (+)-JQ1 COMPOUND; AZEPINE DERIVATIVE; BROMODOMAIN AND EXTRA-TERMINAL DOMAIN PROTEIN, HUMAN; PRKAA1 PROTEIN, HUMAN; PROTEIN; SIGNAL PEPTIDE; SMALL INTERFERING RNA; TRIAZOLE DERIVATIVE; TUMOR PROTEIN; ULK1 PROTEIN, HUMAN;

ACUTE MYELOID LEUKEMIA CELL LINE; APOPTOSIS; ARTICLE; AUTOPHAGOSOME; AUTOPHAGY; CANCER RESISTANCE; CELL PROLIFERATION; CELL SURVIVAL; CELL VIABILITY; CHROMOSOME CONDENSATION; CONTROLLED STUDY; DOWN REGULATION; ENZYME ACTIVATION; ENZYME PHOSPHORYLATION; HUMAN; HUMAN CELL; IN VITRO STUDY; PRIORITY JOURNAL; PROTEIN CLEAVAGE; PROTEIN DEGRADATION; PROTEIN EXPRESSION; RNA INTERFERENCE; SIGNAL TRANSDUCTION; UPREGULATION; ACUTE MYELOID LEUKEMIA; ANTAGONISTS AND INHIBITORS; CANCER STEM CELL; CELL LINEAGE; DRUG EFFECTS; DRUG RESISTANCE; GENE EXPRESSION REGULATION; GENETICS; PATHOLOGY; TUMOR CELL LINE;

AMP-ACTIVATED PROTEIN KINASES; APOPTOSIS; AUTOPHAGY; AUTOPHAGY-RELATED PROTEIN-1 HOMOLOG; AZEPINES; CELL LINE, TUMOR; CELL LINEAGE; DRUG RESISTANCE, NEOPLASM; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; LEUKEMIA, MYELOID, ACUTE; NEOPLASM PROTEINS; NEOPLASTIC STEM CELLS; PROTEINS; RNA, SMALL INTERFERING; SIGNAL TRANSDUCTION; TRIAZOLES;

EID: 85020275929     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-16-1903     Document Type: Article

References (49)

1. Marcucci G, Haferlach T, Dohner H. Molecular genetics of adult acute myeloid leukemia: prognostic and therapeutic implications. J Clin Oncol 2011;29:475-86.
2. Jordan CT. Unique molecular and cellular features of acute myelogenous leukemia stem cells. Leukemia 2002;16:559-62.
3. Jordan CT. The leukemic stem cell. Best Pract Res Clin Haematol 2007;20:13-8.
4. Dorrance AM, Neviani P, Ferenchak GJ, Huang X, Nicolet D, Maharry KS, et al. Targeting leukemia stem cells in vivo with antagomiR-126 nanoparticles in acute myeloid leukemia. Leukemia 2015;29:2143-53.
5. Crews LA, Jamieson CH. Selective elimination of leukemia stem cells: hitting a moving target. Cancer Lett 2013;338:15-22.
6. Chen J, Odenike O, Rowley JD. Leukaemogenesis: more thanmutant genes. Nat Rev Cancer 2010;10:23-36.
7. Dick JE. Stem cell concepts renew cancer research. Blood 2008;112: 4793-807.
8. Belkina AC, Denis GV. BET domain co-regulators in obesity, inflammation and cancer. Nat Rev Cancer 2012;12:465-77.
9. Loven J, Hoke HA, Lin CY, Lau A, Orlando DA, Vakoc CR, et al. Selective inhibition of tumor oncogenes by disruption of super-enhancers. Cell 2013;153:320-34.
10. Zuber J, Shi J, Wang E, Rappaport AR, Herrmann H, Sison EA, et al. RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia. Nature 2011;478:524-8.
11. Delmore JE, Issa GC, Lemieux ME, Rahl PB, Shi J, Jacobs HM, et al. BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell 2011;146:904-17.
12. HerrmannH, Blatt K, Shi J, Gleixner KV, Cerny-Reiterer S, Mullauer L, et al. Small-molecule inhibition of BRD4 as a new potent approach to eliminate leukemic stem- and progenitor cells in acute myeloid leukemia AML. Oncotarget 2012;3:1588-99.
13. Stewart HJ, Horne GA, Bastow S, Chevassut TJ. BRD4 associates with p53 in DNMT3A-mutated leukemia cells and is implicated in apoptosis by the bromodomain inhibitor JQ1. Cancer Med 2013;2:826-35.
14. Fiskus W, Sharma S, Qi J, Valenta JA, Schaub LJ, Shah B, et al. Highly active combination of BRD4 antagonist and histone deacetylase inhibitor against human acute myelogenous leukemia cells. Mol Cancer Ther 2014;13: 1142-54.
15. Dawson MA, Prinjha RK, Dittmann A, Giotopoulos G, Bantscheff M, Chan WI, et al. Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. Nature 2011;478: 529-33.
16. Kim J, Woo AJ, Chu J, Snow JW, Fujiwara Y, Kim CG, et al. A Myc network accounts for similarities between embryonic stem and cancer cell transcription programs. Cell 2010;143:313-24.
17. Coude MM, Braun T, Berrou J, Dupont M, Bertrand S, Masse A, et al. BET inhibitor OTX015 targets BRD2 and BRD4 and decreases c-MYC in acute leukemia cells. Oncotarget 2015;6:17698-712.
18. Ott CJ, Kopp N, Bird L, Paranal RM, Qi J, Bowman T, et al. BET bromodomain inhibition targets both c-Myc and IL7R in high-risk acute lymphoblastic leukemia. Blood 2012;120:2843-52.
19. Conery AR, Centore RC, Spillane KL, Follmer NE, Bommi-Reddy A, Hatton C, et al. Preclinical anticancer efficacy of BET bromodomain inhibitors is determined by the apoptotic response. Cancer Res 2016;76:1313-9.
20. Fong CY, Gilan O, Lam EY, Rubin AF, Ftouni S, Tyler D, et al. BET inhibitor resistance emerges from leukaemia stem cells. Nature 2015; 525:538-42.
21. Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 2009;114:937-51.
22. Byrd JC, Mrozek K, Dodge RK, Carroll AJ, Edwards CG, Arthur DC, et al. Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and LeukemiaGroup B (CALGB 8461). Blood 2002;100:4325-36.
23. Levis M, Small D. FLT3: ITDoes matter in leukemia. Leukemia 2003;17: 1738-52.
24. Schnittger S, Schoch C, Kern W, Mecucci C, Tschulik C, Martelli MF, et al. Nucleophosmin gene mutations are predictors of favorable prognosis in acute myelogenous leukemia with a normal karyotype. Blood 2005;106: 3733-9.
25. Kim JS, Eom JI, Cheong JW, Choi AJ, Lee JK, Yang WI, et al. Protein kinase CK2alpha as an unfavorable prognostic marker and novel therapeutic target in acute myeloid leukemia. Clin Cancer Res 2007;13:1019-28.
26. Vergne I, Roberts E, Elmaoued RA, Tosch V, Delgado MA, Proikas-Cezanne T, et al. Control of autophagy initiation by phosphoinositide 3-phosphatase Jumpy. EMBO J 2009;28:2244-58.
27. Kim YR, Eom JI, Kim SJ, Jeung HK, Cheong JW, Kim JS, et al. Myeloperoxidase expression as a potential determinant of parthenolide-induced apoptosis in leukemia bulk and leukemia stem cells. J Pharmacol Exp Ther 2010;335:389-400.
28. Williams BA, Wang XH, Keating A. Clonogenic assays measure leukemia stem cell killing not detectable by chromium release and flow cytometric cytotoxicity assays. Cytotherapy 2010;12:951-60.
29. She M, Niu X, Chen X, Li J, Zhou M, He Y, et al. Resistance of leukemic stemlike cells in AML cell line KG1a to natural killer cell-mediated cytotoxicity. Cancer Lett 2012;318:173-9.
30. Pedranzini L, Mottadelli F, Ronzoni S, Rossella F, Ferracin M, Magnani I, et al. Differential cytogenomics andmiRNA signature of the Acute Myeloid Leukaemia Kasumi-1 cell line CD34+38- compartment. Leuk Res 2010; 34:1287-95.
31. Costello R, Mallet F, Chambost H, Sainty D, Arnoulet C, Gastaut JA, et al. The immunophenotype of minimally differentiated acute myeloid leukemia (AML-M0): reduced immunogenicity and high frequency of CD34+/CD38+leukemic progenitors. Leukemia 1999;13:1513-8.
32. Lin R, Wang S, Zhao RC. Exosomes from human adipose-derived mesenchymal stem cells promotemigration through Wnt signaling pathway in a breast cancer cell model. Mol Cell Biochem 2013;383:13-20.
33. Pattingre S, Espert L, Biard-Piechaczyk M, Codogno P. Regulation of macroautophagy by mTOR and Beclin 1 complexes. Biochimie 2008;90: 313-23.
34. Liang XH, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H, et al. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 1999;402:672-6.
35. Earnshaw WC, Martins LM, Kaufmann SH.Mammalian caspases: structure, activation, substrates, and functions during apoptosis. Annu Rev Biochem 1999;68:383-424.
36. Egan DF, Shackelford DB, Mihaylova MM, Gelino S, Kohnz RA, Mair W, et al. Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science 2011;331:456-61.
37. Kim J, Kundu M, Viollet B, Guan KL. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol 2011;13:132-41.
38. Nazarko VY, Zhong Q. ULK1 targets Beclin-1 in autophagy. Nat Cell Biol 2013;15:727-8.
39. Wang H, Sharma L, Lu J, Finch P, Fletcher S, Prochownik EV. Structurally diverse c-Myc inhibitors share a common mechanism of action involving ATP depletion. Oncotarget 2015;6:15857-70.
40. Rathert P, Roth M, Neumann T, Muerdter F, Roe JS, Muhar M, et al. Transcriptional plasticity promotes primary and acquired resistance to BET inhibition. Nature 2015;525:543-7.
41. Chittaranjan S, Bortnik S, Dragowska WH, Xu J, Abeysundara N, Leung A, et al. Autophagy inhibition augments the anticancer effects of epirubicin treatment in anthracycline-sensitive and -resistant triple-negative breast cancer. Clin Cancer Res 2014;20:3159-73.
42. Kim Y, Eom JI, Jeung HK, Jang JE, Kim JS, Cheong JW, et al. Induction of cytosine arabinoside-resistant human myeloid leukemia cell death through autophagy regulation by hydroxychloroquine. Biomed Pharmacother 2015;73:87-96.
43. Toh PP, Luo S, Menzies FM, Rasko T, Wanker EE, Rubinsztein DC. Myc inhibition impairs autophagosome formation. Hum Mol Genet 2013; 22:5237-48.
44. Roach PJ. AMPK ->ULK1 ->autophagy. Mol Cell Biol 2011;31:3082-4.
45. Xie CM, Liu XY, Sham KW, Lai JM, Cheng CH. Silencing of EEF2K (eukaryotic elongation factor-2 kinase) reveals AMPK-ULK1-dependent autophagy in colon cancer cells. Autophagy 2014;10:1495-508.
46. Tian W, Li W, Chen Y, Yan Z, Huang X, Zhuang H, et al. Phosphorylation of ULK1 by AMPK regulates translocation of ULK1 to mitochondria and mitophagy. FEBS Lett 2015;589:1847-54.
47. Saito Y, Chapple RH, Lin A, Kitano A, Nakada D. AMPK protects leukemiainitiating cells in myeloid leukemias from metabolic stress in the bone marrow. Cell Stem Cell 2015;17:585-96.
48. Fowler T, Ghatak P, Price DH, Conaway R, Conaway J, Chiang CM, et al. Regulation of MYC expression and differential JQ1 sensitivity in cancer cells. PLoS One 2014;9:e87003.
49. Trabucco SE, Gerstein RM, Evens AM, Bradner JE, Shultz LD, Greiner DL, et al. Inhibition of bromodomain proteins for the treatment of human diffuse large B-cell lymphoma. Clin Cancer Res 2015;21:113-22.