Highly active combination of BRD4 antagonist and histone deacetylase inhibitor against human acute myelogenous leukemia cells

Molecular Cancer Therapeutics

Volumn 13, Issue 5, 2014, Pages 1142-1154

  Fiskus, Warren ^a   Sharma, Sunil ^b   Qi, Jun ^c   Valenta, John A ^a   Schaub, Leasha J ^a   Shah, Bhavin ^a   Peth, Karissa ^a   Portier, Bryce P ^a   Rodriguez, Melissa ^a   Devaraj, Santhana G T ^a   Zhan, Ming ^a   Sheng, Jianting ^a   Iyer, Swaminathan P ^a   Bradner, James E ^c   Bhalla, Kapil N ^a  

^a HOUSTON METHODIST RESEARCH INSTITUTE   (United States)

^b UNIVERSITY OF UTAH   (United States)

^c DANA FARBER CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; BIM PROTEIN; BRD4 ANTAGONIST; BRD4 PROTEIN; CD135 ANTIGEN; CD34 ANTIGEN; CYCLIN DEPENDENT KINASE 6; JQ 1; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE; NUCLEOPHOSMIN; PANOBINOSTAT; PROTEIN; PROTEIN BCL 2; PROTEIN INHIBITOR; PROTEIN P21; RNA POLYMERASE II; SHORT HAIRPIN RNA; UNCLASSIFIED DRUG; APOPTOSIS REGULATORY PROTEIN; BCL-2-LIKE PROTEIN 11; BRD4 PROTEIN, HUMAN; HISTONE DEACETYLASE INHIBITOR; HYDROXAMIC ACID; INDOLE DERIVATIVE; MEMBRANE PROTEIN; MESSENGER RNA; NUCLEAR PROTEIN; ONCOPROTEIN; PROTEIN BINDING; TRANSCRIPTION FACTOR;

ACUTE GRANULOCYTIC LEUKEMIA; ANIMAL EXPERIMENT; APOPTOSIS; ARTICLE; BLAST PROGENITOR CELL; CANCER SURVIVAL; CELL VIABILITY; DOWN REGULATION; DRUG POTENTIATION; ENANTIOMER; FLOW CYTOMETRY; GENE EXPRESSION; HEMATOPOIETIC STEM CELL; HISTONE ACETYLATION; HUMAN; HUMAN CELL; IMMUNOBLOTTING; MOUSE; MYELOID LEUKEMIA CELL LINE; NONHUMAN; ONCOGENE C MYC; OVERALL SURVIVAL; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN EXPRESSION; REAL TIME POLYMERASE CHAIN REACTION; SCANNING ELECTRON MICROSCOPY; TRANSCRIPTION ELONGATION; UPREGULATION; ANIMAL; ANTAGONISTS AND INHIBITORS; CANCER STEM CELL; CELL CYCLE; CLUSTER ANALYSIS; DISEASE MODEL; DRUG EFFECTS; DRUG SCREENING; FEMALE; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; MORTALITY; ONCOGENE MYC; PATHOLOGY; PROTO ONCOGENE; TUMOR CELL LINE;

ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; APOPTOSIS REGULATORY PROTEINS; CELL CYCLE; CELL LINE, TUMOR; CLUSTER ANALYSIS; DISEASE MODELS, ANIMAL; DRUG SYNERGISM; FEMALE; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION, LEUKEMIC; GENES, BCL-2; GENES, MYC; HEMATOPOIETIC STEM CELLS; HISTONE DEACETYLASE INHIBITORS; HUMANS; HYDROXAMIC ACIDS; INDOLES; LEUKEMIA, MYELOID, ACUTE; MEMBRANE PROTEINS; MICE; NEOPLASTIC STEM CELLS; NUCLEAR PROTEINS; ONCOGENE PROTEINS, FUSION; PROMOTER REGIONS, GENETIC; PROTEIN BINDING; PROTO-ONCOGENE PROTEINS; RNA, MESSENGER; TRANSCRIPTION FACTORS; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84899893338     PISSN: 15357163     EISSN: 15388514     Source Type: Journal    
DOI: 10.1158/1535-7163.MCT-13-0770     Document Type: Article

References (33)

1. Bhalla KN. Epigenetic and chromatin modifiers as targeted therapy of hematologic malignancies. J Clin Oncol 2005;23:3971-93.
2. Shen H, Laird PW. Interplay between the cancer genome and epigenome. Cell 2013;153:38-55.
3. Arrowsmith CH, Bountra C, Fish PV, Lee K, Schapira M. Epigenetic protein families: a new frontier for drug discovery. Nat Rev Drug Disc 2012;11:384-400.
4. Wu SY, Chiang CM. The double bromodomain-containing chromatin adaptor Brd4 and transcriptional regulation. J Biol Chem 2007;282: 13141-5.
5. Belkina AC, Denis GV. BET domain co-regulators in obesity, inflammation and cancer. Nat Rev Cancer 2012;12:465-77.
6. Patel MC, Debrosse M, Smith M, Dey A, Huynh W, Sarai N, et al. BRD4 coordinates recruitment of pause release factor P-TEFb and the pausing complex NELF/DSIF to regulate transcription elongation of interferon-stimulated genes. Mol Cell Biol 2013;33:2497-507.
7. 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.
8. Lockwood WW, Zejnullahu K, Bradner JE, Varmus H. Sensitivity of human lung adenocarcinoma cell lines to targeted inhibition of BET epigenetic signaling proteins. Proc Natl Acad Sci U S A 2012;109: 19408-13.
9. Lee TI, Young RA. Transcriptional regulation and its misregulation in disease. Cell 2013;152:1237-51.
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. Filippakopoulos P, Qi J, Picaud S, Shen Y, Smith WB, Fedorov O, et al. Selective inhibition of BET bromodomains. Nature 2010;468:1067-73.
12. Mirguet O, Lamotte Y, Donche F, Toum J, Gellibert F, Bouillot A, et al. From ApoA1 upregulation to BET family bromodomain inhibition: discovery of I-BET151. Bioorg Med Chem Lett 2012;22:2963-7.
13. Seal J, Lamotte Y, Donche F, Bouillot A, Mirguet O, Gellibert F, et al. Identification of a novel series of BET family bromodomain inhibitors: binding mode and profile of I-BET151 (GSK1210151A). Bioorg Med Chem Lett 2012;22:2968-72.
14. 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.
15. Mertz JA, Conery AR, Bryant BM, Sandy P, Balasubramanian S, Mele DA, et al. Targeting MYC dependence in cancer by inhibiting BET bromodomains. Proc Natl Acad Sci U S A 2011;108:16669-74.
16. 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.
17. George P, Bali P, Annavarapu S, Scuto A, Fiskus W, Guo F, et al. Combination of the histone deacetylase inhibitor LBH589 and the hsp90 inhibitor 17-AAG is highly active against human CML-BC cells and AML cells with activating mutation of FLT-3. Blood 2005;105: 1768-76.
18. Fiskus W, Verstovsek S, Manshouri T, Smith JE, Peth K, Abhyankar S, et al. Dual PI3K/AKT/mTOR inhibitor BEZ235 synergistically enhances the activity of JAK2 inhibitor against cultured and primary human myeloproliferative neoplasm cells. Mol Cancer Ther 2013;12:577-88.
19. Fiskus W, Wang Y, Sreekumar A, Buckley KM, Shi H, Jillella A, et al. Combined epigenetic therapy with the histone methyltransferase EZH2 inhibitor 3-deazaneplanocin A and the histone deacetylase inhibitor panobinostat against human AML cells. Blood 2009;114: 2733-43.
20. Balusu R, Fiskus W, Rao R, Chong DG, Nalluri S, Mudunuru U, et al. Targeting levels or oligomerization of nucleophosmin 1 induces differentiation and loss of survival of humanAMLcells with mutant NPM1. Blood 2011;118:3096-106.
21. Chou TC, Talalay P. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul 1984;22:27-55.
22. Schnittger S, Bacher U, Kern W, Alpermann T, Haferlach C, Haferlach T. Prognostic impact of FLT3-ITD load inNPM1mutated acute myeloid leukemia. Leukemia 2011;25:1297-304.
23. Lin CY, Loven J, Rahl PB, Paranal RM, Burge CB, Bradner JE, et al. Transcriptional amplification in tumor cells with elevated c-Myc. Cell 2012;151:56-67.
24. Deangelo DJ, Spencer A, Bhalla KN, Prince HM, Fischer T, Kindler T, et al. Phase Ia/II, two-arm, open-label, dose-escalation study of oral panobinostat administered via two dosing schedules in patients with advanced hematologic malignancies. Leukemia 2013;27:1628-36
25. Dang CV. MYC on the path to cancer. Cell 2012;149:22-35.
26. Kindler T, Lipka DB, Fischer T. FLT3 as a therapeutic target in AML: still challenging after all these years. Blood 2010;116:5089-102.
27. Gale RE, Green C, Allen C, Mead AJ, Burnett AK, Hills RK, et al. The impact of FLT3 internal tandem duplication mutant level, number, size, and interaction with NPM1 mutations in a large cohort of young adult patients with acute myeloid leukemia. Blood 2008;111:2776-84.
28. Levis M. FLT3/ITD AML and the law of unintended consequences. Blood 2011;117:6987-90.
29. Smith CC, Wang Q, Chin CS, Salerno S, Damon LE, Levis MJ, et al. Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia. Nature 2012;485:260-3.
30. Eppert K, Takenaka K, Lechman ER, Waldron L, Nilsson B, van Galen P, et al. Stem cell gene expression programs influence clinical outcome in human leukemia. Nat Med 2011;17:1086-93.
31. Buss EC,Ho AD. Leukemia stem cells. Int J Cancer 2011;129:2328-36.
32. Zou Z, Huang B, Wu X, Zhang H, Qi J, Bradner J, et al. Brd4 maintains constitutively active NF-kappaB in cancer cells by binding to acetylated RelA. Oncogene. Epub 2013 May 20.
33. Zhang G, Liu R, Zhong Y, Plotnikov AN, Zhang W, Zeng L, et al. Downregulation of NF-kappaB transcriptional activity in HIV-associated kidney disease by BRD4 inhibition. J Biol Chem 2012;287:28840-51.