Functional interdependence of BRD4 and DOT1L in MLL leukemia

Nature Structural and Molecular Biology

Volumn 23, Issue 7, 2016, Pages 673-681

  Gilan, Omer ^a,b   Lam, Enid Y N ^a,b   Becher, Isabelle ^c   Lugo, Dave ^d   Cannizzaro, Ester ^e   Joberty, Gerard ^c   Ward, Aoife ^c   Wiese, Meike ^e   Fong, Chun Yew ^a,b   Ftouni, Sarah ^a   Tyler, Dean ^a,b   Stanley, Kym ^a   MacPherson, Laura ^a   Weng, Chen Fang ^a   Chan, Yih Chih ^a   Ghisi, Margherita ^a   Smil, David ^f   Carpenter, Christopher ^g   Brown, Peter ^f   Garton, Neil ^d   Blewitt, Marnie E ^b,h   Bannister, Andrew J ^e   Kouzarides, Tony ^e   Huntly, Brian J P ^i,j   Johnstone, Ricky W ^a,b   Drewes, Gerard ^c   Dawson, Sarah Jane ^a,b   Arrowsmith, Cheryl H ^f,k   Grandi, Paola ^c   Prinjha, Rab K ^d   Dawson, Mark A ^a,b   more..

^a PETER MACCALLUM CANCER CENTRE   (Australia)

^b UNIVERSITY OF MELBOURNE   (Australia)

^c GLAXOSMITHKLINE   (Germany)

^d GLAXOSMITHKLINE   (United Kingdom)

^e UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^f UNIVERSITY OF TORONTO   (Canada)

^g GLAXOSMITHKLINE   (United States)

^h WALTER AND ELIZA HALL INSTITUTE OF MEDICAL RESEARCH   (Australia)

ⁱ UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^j University of Cambridge   (United Kingdom)

^k PRINCESS MARGARET HOSPITAL   (Canada)

more..

Author keywords

[No Author keywords available]

Indexed keywords

BROMODOMAIN CONTAINING PROTEIN 4; DISRUPTOR OF TELOMERIC SILENCING 1 LIKE; HISTONE H3; HISTONE H4; PROTEIN; UNCLASSIFIED DRUG; BRD4 PROTEIN, HUMAN; CHROMATIN; DOT1L PROTEIN, HUMAN; HISTONE; METHYLTRANSFERASE; NUCLEAR PROTEIN; PROTEIN BINDING; SMALL INTERFERING RNA; TRANSCRIPTION FACTOR;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CANCER PROGNOSIS; CHROMATIN; CONTROLLED STUDY; DOWN REGULATION; ENHANCER REGION; GENE EXPRESSION; GENETIC TRANSCRIPTION; HEMATOPOIETIC CELL; HISTONE MODIFICATION; HUMAN; HUMAN CELL; IMMUNOPRECIPITATION; LEUKEMIA; LEUKEMIA CELL; MIXED LINEAGE LEUKEMIA; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN ACETYLATION; PROTEIN TARGETING; PROTEOMICS; SIZE EXCLUSION CHROMATOGRAPHY; ACETYLATION; ACUTE BIPHENOTYPIC LEUKEMIA; ANIMAL; ANTAGONISTS AND INHIBITORS; B LYMPHOCYTE; C57BL MOUSE; CELL PROLIFERATION; CHEMISTRY; CLINICAL TRIAL (TOPIC); DISEASE MODEL; FEMALE; GENE EXPRESSION REGULATION; GENETICS; MALE; METABOLISM; PATHOLOGY; PRIMARY CELL CULTURE; PROCEDURES; SIGNAL TRANSDUCTION; T LYMPHOCYTE;

ACETYLATION; ANIMALS; B-LYMPHOCYTES; CELL PROLIFERATION; CHROMATIN; CLINICAL TRIALS AS TOPIC; DISEASE MODELS, ANIMAL; FEMALE; GENE EXPRESSION REGULATION, LEUKEMIC; HISTONES; HUMANS; LEUKEMIA, BIPHENOTYPIC, ACUTE; MALE; METHYLTRANSFERASES; MICE; MICE, INBRED C57BL; NUCLEAR PROTEINS; PRIMARY CELL CULTURE; PROTEIN BINDING; PROTEOMICS; RNA, SMALL INTERFERING; SIGNAL TRANSDUCTION; T-LYMPHOCYTES; TRANSCRIPTION FACTORS; TRANSCRIPTION, GENETIC;

EID: 84977604356     PISSN: 15459993     EISSN: 15459985     Source Type: Journal    
DOI: 10.1038/nsmb.3249     Document Type: Article

References (72)

1. Stratton, M.R., Campbell, P.J. & Futreal, P.A. The cancer genome. Nature 458, 719-724 (2009).
2. Dawson, M.A. & Kouzarides, T. Cancer epigenetics: from mechanism to therapy. Cell 150, 12-27 (2012).
3. Patel, J.P. et al. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N. Engl. J. Med. 366, 1079-1089 (2012).
4. Cancer Genome Atlas Research Network. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N. Engl. J. Med. 368, 2059-2074 (2013).
5. Cai, S.F., Chen, C.W. & Armstrong, S.A. Drugging chromatin in cancer: recent advances and novel approaches. Mol. Cell 60, 561-570 (2015).
6. Dawson, M.A., Kouzarides, T. & Huntly, B.J. Targeting epigenetic readers in cancer. N. Engl. J. Med. 367, 647-657 (2012).
7. Rathert, P. et al. Transcriptional plasticity promotes primary and acquired resistance to BET inhibition. Nature 525, 543-547 (2015).
8. Prebet, T. et al. Prolonged administration of azacitidine with or without entinostat for myelodysplastic syndrome and acute myeloid leukemia with myelodysplasia-related changes: results of the US Leukemia Intergroup trial E1905. J. Clin. Oncol. 32, 1242-1248 (2014).
9. Issa, J.P. et al. Results of phase 2 randomized study of low-dose decitabine with or without valproic acid in patients with myelodysplastic syndrome and acute myelogenous leukemia. Cancer 121, 556-561 (2015).
10. Yu, B.D., Hess, J.L., Horning, S.E., Brown, G.A. & Korsmeyer, S.J. Altered Hox expression and segmental identity in Mll-mutant mice. Nature 378, 505-508 (1995).
11. McMahon, K.A. et al. Mll has a critical role in fetal and adult hematopoietic stem cell self-renewal. Cell Stem Cell 1, 338-345 (2007).
12. Jude, C.D. et al. Unique and independent roles for MLL in adult hematopoietic stem cells and progenitors. Cell Stem Cell 1, 324-337 (2007).
13. Neff, T. & Armstrong, S.A. Recent progress toward epigenetic therapies: the example of mixed lineage leukemia. Blood 121, 4847-4853 (2013).
14. Dawson, M.A. et al. Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. Nature 478, 529-533 (2011).
15. Daigle, S.R. et al. Selective killing of mixed lineage leukemia cells by a potent small-molecule DOT1L inhibitor. Cancer Cell 20, 53-65 (2011).
16. Grembecka, J. et al. Menin-MLL inhibitors reverse oncogenic activity of MLL fusion proteins in leukemia. Nat. Chem. Biol. 8, 277-284 (2012).
17. Harris, W.J. et al. The histone demethylase KDM1A sustains the oncogenic potential of MLL-AF9 leukemia stem cells. Cancer Cell 21, 473-487 (2012).
18. Mohan, M., Lin, C., Guest, E. & Shilatifard, A. Licensed to elongate: a molecular mechanism for MLL-based leukaemogenesis. Nat. Rev. Cancer 10, 721-728 (2010).
19. Biswas, D. et al. Function of leukemogenic mixed lineage leukemia 1 (MLL) fusion proteins through distinct partner protein complexes. Proc. Natl. Acad. Sci. USA 108, 15751-15756 (2011).
20. Bitoun, E., Oliver, P.L. & Davies, K.E. The mixed-lineage leukemia fusion partner AF4 stimulates RNA polymerase II transcriptional elongation and mediates coordinated chromatin remodeling. Hum. Mol. Genet. 16, 92-106 (2007).
21. Lin, C. et al. AFF4, a component of the ELL/P-TEFb elongation complex and a shared subunit of MLL chimeras, can link transcription elongation to leukemia. Mol. Cell 37, 429-437 (2010).
22. Mohan, M. et al. Linking H3K79 trimethylation to Wnt signaling through a novel Dot1-containing complex (DotCom). Genes Dev. 24, 574-589 (2010).
23. Mueller, D. et al. A role for the MLL fusion partner ENL in transcriptional elongation and chromatin modification. Blood 110, 4445-4454 (2007).
24. Mueller, D. et al. Misguided transcriptional elongation causes mixed lineage leukemia. PLoS Biol. 7, e1000249 (2009).
25. Yokoyama, A., Lin, M., Naresh, A., Kitabayashi, I. & Cleary, M.L. A higher-order complex containing AF4 and ENL family proteins with P-TEFb facilitates oncogenic and physiologic MLL-dependent transcription. Cancer Cell 17, 198-212 (2010).
26. Yu, W. et al. Catalytic site remodelling of the DOT1L methyltransferase by selective inhibitors. Nat. Commun. 3, 1288 (2012).
27. Zuber, J. et al. RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia. Nature 478, 524-528 (2011).
28. Chen, C.W. et al. DOT1L inhibits SIRT1-mediated epigenetic silencing to maintain leukemic gene expression in MLL-rearranged leukemia. Nat. Med. 21, 335-343 (2015).
29. Shi, J. et al. Discovery of cancer drug targets by CRISPR-Cas9 screening of protein domains. Nat. Biotechnol. 33, 661-667 (2015).
30. Bernt, K.M. et al. MLL-rearranged leukemia is dependent on aberrant H3K79 methylation by DOT1L. Cancer Cell 20, 66-78 (2011).
31. Fong, C.Y. et al. BET inhibitor resistance emerges from leukaemia stem cells. Nature 525, 538-542 (2015).
32. Nguyen, A.T. & Zhang, Y. The diverse functions of Dot1 and H3K79 methylation. Genes Dev. 25, 1345-1358 (2011).
33. Lovén, J. et al. Selective inhibition of tumor oncogenes by disruption of super-enhancers. Cell 153, 320-334 (2013).
34. Pott, S. & Lieb, J.D. What are super-enhancers? Nat. Genet. 47, 8-12 (2015).
35. Yang, L. et al. lncRNA-dependent mechanisms of androgen-receptor-regulated gene activation programs. Nature 500, 598-602 (2013).
36. LeRoy, G. et al. Proteogenomic characterization and mapping of nucleosomes decoded by Brd and HP1 proteins. Genome Biol. 13, R68 (2012).
37. Zhao, R., Nakamura, T., Fu, Y., Lazar, Z. & Spector, D.L. Gene bookmarking accelerates the kinetics of post-mitotic transcriptional re-activation. Nat. Cell Biol. 13, 1295-1304 (2011).
38. Lee, J.S., Smith, E. & Shilatifard, A. The language of histone crosstalk. Cell 142, 682-685 (2010).
39. Shankar, D.B. et al. The role of CREB as a proto-oncogene in hematopoiesis and in acute myeloid leukemia. Cancer Cell 7, 351-362 (2005).
40. Henry, R.A., Kuo, Y.M. & Andrews, A.J. Differences in specificity and selectivity between CBP and p300 acetylation of histone H3 and H3/H4. Biochemistry 52, 5746-5759 (2013).
41. Roe, J.S., Mercan, F., Rivera, K., Pappin, D.J. & Vakoc, C.R. BET bromodomain inhibition suppresses the function of hematopoietic transcription factors in acute myeloid leukemia. Mol. Cell 58, 1028-1039 (2015).
42. Lavallée, V.P. et al. The transcriptomic landscape and directed chemical interrogation of MLL-rearranged acute myeloid leukemias. Nat. Genet. 47, 1030-1037 (2015).
43. Jo, S.Y., Granowicz, E.M., Maillard, I., Thomas, D. & Hess, J.L. Requirement for Dot1l in murine postnatal hematopoiesis and leukemogenesis by MLL translocation. Blood 117, 4759-4768 (2011).
44. Nguyen, A.T., Taranova, O., He, J. & Zhang, Y. DOT1L, the H3K79 methyltransferase, is required for MLL-AF9-mediated leukemogenesis. Blood 117, 6912-6922 (2011).
45. Bannister, A.J. & Kouzarides, T. Regulation of chromatin by histone modifications. Cell Res. 21, 381-395 (2011).
46. Dawson, M.A. et al. Recurrent mutations, including NPM1c, activate a BRD4-dependent core transcriptional program in acute myeloid leukemia. Leukemia 28, 311-320 (2014).
47. McLean, C.M., Karemaker, I.D. & van Leeuwen, F. The emerging roles of DOT1L in leukemia and normal development. Leukemia 28, 2131-2138 (2014).
48. Shi, J. & Vakoc, C.R. The mechanisms behind the therapeutic activity of BET bromodomain inhibition. Mol. Cell 54, 728-736 (2014).
49. Sarkaria, S.M., Christopher, M.J., Klco, J.M. & Ley, T.J. Primary acute myeloid leukemia cells with IDH1 or IDH2 mutations respond to a DOT1L inhibitor in vitro. Leukemia 28, 2403-2406 (2014).
50. Jonkers, I. & Lis, J.T. Getting up to speed with transcription elongation by RNA polymerase II. Nat. Rev. Mol. Cell Biol. 16, 167-177 (2015).
51. Smith, E. & Shilatifard, A. Transcriptional elongation checkpoint control in development and disease. Genes Dev. 27, 1079-1088 (2013).
52. Herait, P.E. et al. BET-bromodomain inhibitor OTX015 shows clinically meaningful activity at nontoxic doses: interim results of an ongoing phase I trial in hematologic malignancies. Cancer Res. 74, CT231 (2014).
53. Stein, E.M. et al. The DOT1L inhibitor EPZ-5676: safety and activity in relapsed/refractory patients with mll-rearranged leukemia. Blood 124, 387 (2014).
54. Kruse, U. et al. Chemoproteomics-based kinome profiling and target deconvolution of clinical multi-kinase inhibitors in primary chronic lymphocytic leukemia cells. Leukemia 25, 89-100 (2011).
55. Savitski, M.M. et al. Tracking cancer drugs in living cells by thermal profiling of the proteome. Science 346, 1255784 (2014).
56. Werner, T. et al. High-resolution enabled TMT 8-plexing. Anal. Chem. 84, 7188-7194 (2012).
57. Savitski, M.M. et al. Delayed fragmentation and optimized isolation width settings for improvement of protein identification and accuracy of isobaric mass tag quantification on Orbitrap-type mass spectrometers. Anal. Chem. 83, 8959-8967 (2011).
58. Savitski, M.M. et al. Targeted data acquisition for improved reproducibility and robustness of proteomic mass spectrometry assays. J. Am. Soc. Mass Spectrom. 21, 1668-1679 (2010).
59. Savitski, M.M. et al. Measuring and managing ratio compression for accurate iTRAQ/TMT quantification. J. Proteome Res. 12, 3586-3598 (2013).
60. Robinson, M.D., McCarthy, D.J. & Smyth, G.K. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26, 139-140 (2010).
61. Benjamini, Y. & Hochberg, Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. R. Stat. Soc. Series B Stat. Methodol. 57, 289-300 (1995).
62. Anders, S. & Huber, W. Differential expression analysis for sequence count data. Genome Biol. 11, R106 (2010).
63. Wu, D. et al. ROAST: rotation gene set tests for complex microarray experiments. Bioinformatics 26, 2176-2182 (2010).
64. Langmead, B. & Salzberg, S.L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357-359 (2012).
65. Zhang, Y. et al. Model-based analysis of ChIP-Seq (MACS). Genome Biol. 9, R137 (2008).
66. Robinson, J.T. et al. Integrative genomics viewer. Nat. Biotechnol. 29, 24-26 (2011).
67. Quinlan, A.R. & Hall, I.M. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26, 841-842 (2010).
68. Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl. Acad. Sci. USA 102, 15545-15550 (2005).
69. Wickham, H. ggplot2: Elegant Graphics for Data Analysis (Springer, 2009).
70. Tsirigos, A., Haiminen, N., Bilal, E. & Utro, F. GenomicTools: a computational platform for developing high-throughput analytics in genomics. Bioinformatics 28, 282-283 (2012).
71. Rädle, B. et al. Metabolic labeling of newly transcribed RNA for high resolution gene expression profiling of RNA synthesis, processing and decay in cell culture. J. Vis. Exp. 78, e50195 (2013).
72. Bailey, T.L. & Machanick, P. Inferring direct DNA binding from ChIP-seq. Nucleic Acids Res. 40, e128 (2012).