Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia

Nature

Volumn 478, Issue 7370, 2011, Pages 529-533

  Dawson, Mark A ^a,b   Prinjha, Rab K ^c   Dittmann, Antje ^c   Giotopoulos, George ^a   Bantscheff, Marcus ^c   Chan, Wai In ^a   Robson, Samuel C ^b   Chung, Chun Wa ^c   Hopf, Carsten ^c   Savitski, Mikhail M ^c   Huthmacher, Carola ^c   Gudgin, Emma ^a   Lugo, Dave ^c   Beinke, Soren ^c   Chapman, Trevor D ^c   Roberts, Emma J ^c   Soden, Peter E ^c   Auger, Kurt R ^d   Mirguet, Olivier ^e   Doehner, Konstanze ^f   Delwel, Ruud ^g   Burnett, Alan K ^h   Jeffrey, Phillip ^c   Drewes, Gerard ^c   Lee, Kevin ^c   Huntly, Brian J P ^a   Kouzarides, Tony ^b   more..

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^b UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^c GLAXOSMITHKLINE   (United Kingdom)

^d GLAXOSMITHKLINE   (United States)

^e Glaxo Smith Kline R and D   (France)

^f UNIVERSITY HOSPITAL ULM   (Germany)

^g ERASMUS MEDICAL CENTER   (Netherlands)

^h CARDIFF UNIVERSITY SCHOOL OF MEDICINE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; CYCLIN DEPENDENT KINASE 6; GSK 1210151A; MIXED LINEAGE LEUKEMIA PROTEIN; PROTEIN BCL 2; UNCLASSIFIED DRUG;

APOPTOSIS; BLOOD; CANCER; CYTOLOGY; DISEASE TREATMENT; DNA; ENZYME ACTIVITY; GENOMICS; INHIBITION; PHENOTYPE; PROTEIN; PROTEOMICS; PUBLIC HEALTH; RODENT; SURVIVAL;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CANCER CELL CULTURE; CANCER CHEMOTHERAPY; CELL CYCLE ARREST; CHROMATIN; CONTROLLED STUDY; DRUG EFFICACY; EPIGENETICS; GENE FUNCTION; HUMAN; HUMAN CELL; IN VIVO STUDY; LEUKEMIA; MOUSE; NONHUMAN; ONCOGENE C MYC; PHENOTYPE; PRIORITY JOURNAL; PROTEOMICS;

ANIMALS; CELL LINE, TUMOR; CHROMATIN; CHROMATIN IMMUNOPRECIPITATION; DISEASE MODELS, ANIMAL; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION, NEOPLASTIC; HETEROCYCLIC COMPOUNDS WITH 4 OR MORE RINGS; HUMANS; LEUKEMIA, MYELOID, ACUTE; MICE; MODELS, MOLECULAR; MULTIPROTEIN COMPLEXES; MYELOID-LYMPHOID LEUKEMIA PROTEIN; ONCOGENE PROTEINS, FUSION; PROTEIN BINDING; PROTEOMICS; TRANSCRIPTION FACTORS; TRANSCRIPTION, GENETIC;

MURINAE;

EID: 80054984945     PISSN: 00280836     EISSN: 14764687     Source Type: Journal    
DOI: 10.1038/nature10509     Document Type: Article

References (21)

1. Krivtsov, A. V. & Armstrong, S. A. MLL translocations, histone modifications and leukaemia stem-cell development. Nature Rev. Cancer 7, 823-833 (2007). (Pubitemid 350006257)
2. 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).
3. 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).
4. Milne, T. A. et al.Multiple interactions recruit MLL1 andMLL1 fusion proteins to the HOXA9 locus in leukemogenesis. Mol. Cell 38, 853-863 (2010).
5. Muntean, A. G. et al. The PAF complex synergizes with MLL fusion proteins at HOX loci to promote leukemogenesis. Cancer Cell 17, 609-621 (2010).
6. Rodríguez-Paredes, M. & Esteller, M. Cancer epigenetics reaches mainstream oncology. Nature Med. 17, 330-339 (2011).
7. Nicodeme, E. et al. Suppression of inflammation by a synthetic histone mimic. Nature 468, 1119-1123 (2010).
8. Filippakopoulos, P. et al. Selective inhibition of BET bromodomains. Nature 468, 1067-1073 (2010).
9. Chung, C. W. et al. Discovery and characterization of small molecule inhibitors of the BET family bromodomains. J. Med. Chem. 54, 3827-3838 (2011).
10. Bantscheff, M. et al. Chemoproteomics profiling of HDAC inhibitors reveals selective targeting of HDAC complexes. Nature Biotechnol. 29, 255-265 (2011).
11. Jang, M. K. et al. The bromodomain protein Brd4 is a positive regulatory component of P-TEFbandstimulatesRNApolymerase II-dependent transcription. Mol. Cell 19, 523-534 (2005).
12. Maruyama, T. et al. A mammalian bromodomain protein, Brd4, interacts with replication factor C and inhibits progression to S phase. Mol. Cell. Biol. 22, 6509-6520 (2002).
13. Yang, Z. et al. Recruitment of P-TEFb for stimulation of transcriptional elongation by the bromodomain protein Brd4. Mol. Cell 19, 535-545 (2005). (Pubitemid 41140010)
14. Somervaille, T. C. et al. Hierarchical maintenance of MLL myeloid leukemia stem cells employs a transcriptional programshared with embryonic rather than adult stem cells. Cell Stem Cell 4, 129-140 (2009).
15. Wang, J. et al. Conditional MLL-CBP targets GMP and models therapy-related myeloproliferative disease. EMBO J. 24, 368-381 (2005). (Pubitemid 40216141)
16. Robinson, B. W. et al. Abundant anti-apoptotic BCL-2 is a molecular target in leukaemias with t(4;11) translocation. Br. J. Haematol. 141, 827-839 (2008). (Pubitemid 351724853)
17. Wang, Q. F. et al. MLL fusion proteins preferentially regulate a subset of wild-type MLL target genes in the leukemic genome. Blood 117, 6895-6905 (2011).
18. O'Farrell, A. M. et al. SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo. Blood 101, 3597-3605 (2003).
19. Zuber, J. et al.RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia. Nature doi:10.1038/nature10334 (this issue).
20. Martinez-Garcia, E. et al. The MMSET histone methyl transferase switches global histone methylation and alters gene expression in t(4;14)multiplemyeloma cells. Blood 117, 211-220 (2011).
21. Dawson, M. A. et al. JAK2 phosphorylates histone H3Y41 and excludes HP1a from chromatin. Nature 461, 819-822 (2009).