Epigenetic therapies by targeting aberrant histone methylome in AML: Molecular mechanisms, current preclinical and clinical development

Oncogene

Volumn 36, Issue 13, 2017, Pages 1753-1759

  Tsai, C T ^a   So, C W E ^a  

^a Division of Psychosis Studies   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; HISTONE DEMETHYLASE; HISTONE METHYLTRANSFERASE; HISTONE; HISTONE LYSINE METHYLTRANSFERASE; PROTEIN BINDING;

ACUTE MYELOID LEUKEMIA; CANCER GENE THERAPY; DNA METHYLATION; DRUG TARGETING; EPIGENETICS; HISTONE ACETYLATION; HISTONE METHYLATION; HUMAN; MOLECULAR BIOLOGY; MOLECULAR INTERACTION; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PRECLINICAL STUDY; PRIORITY JOURNAL; PROSPECTIVE STUDY; REVIEW; TREATMENT RESPONSE; ACETYLATION; ANIMAL; ANTAGONISTS AND INHIBITORS; CLINICAL STUDY; DRUG EFFECTS; GENETIC EPIGENESIS; GENETICS; LEUKEMIA, MYELOID, ACUTE; METABOLISM; MOLECULARLY TARGETED THERAPY; SIGNAL TRANSDUCTION; TREATMENT OUTCOME;

ACETYLATION; ANIMALS; ANTINEOPLASTIC AGENTS; CLINICAL STUDIES AS TOPIC; DNA METHYLATION; DRUG EVALUATION, PRECLINICAL; EPIGENESIS, GENETIC; HISTONE DEMETHYLASES; HISTONE-LYSINE N-METHYLTRANSFERASE; HISTONES; HUMANS; LEUKEMIA, MYELOID, ACUTE; MOLECULAR TARGETED THERAPY; PROTEIN BINDING; SIGNAL TRANSDUCTION; TREATMENT OUTCOME;

EID: 84990945310     PISSN: 09509232     EISSN: 14765594     Source Type: Journal    
DOI: 10.1038/onc.2016.315     Document Type: Review

References (75)

1. Burnett A, Wetzler M, Lowenberg B. Therapeutic advances in acute myeloid leukemia. J Clin Oncol 2011; 29: 487-494.
2. Ferrara F, Schiffer CA. Acute myeloid leukaemia in adults. Lancet 2013; 381: 484-495.
3. Zeisig BB, Kulasekararaj AG, Mufti GJ, So CW. SnapShot: acute myeloid leukemia. Cancer Cell 2012; 22: 698-698.e1.
4. Zeisig BB, So CW. Cellular and molecular basis of KMT2A/MLL leukaemias: from transformation mechanisms to novel therapeutic strategies. In: Rowley JD, Le Beau MM, Rabbitts TH (eds). Chromosomal Translocations and Genome Rearrangements in Cancer. Springer: NY, USA, 2016, pp 223-250.
5. Shlush LI, Zandi S, Mitchell A, Chen WC, Brandwein JM, Gupta V et al. Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia. Nature 2014; 506: 328-333.
6. Kronke J, Bullinger L, Teleanu V, Tschurtz F, Gaidzik VI, Kuhn MW et al. Clonal evolution in relapsed NPM1-mutated acute myeloid leukemia. Blood 2013; 122: 100-108.
7. Hou HA, Kuo YY, Liu CY, Chou WC, Lee MC, Chen CY et al. DNMT3A mutations in acute myeloid leukemia: stability during disease evolution and clinical implications. Blood 2012; 119: 559-568.
8. Egger G, Liang G, Aparicio A, Jones PA. Epigenetics in human disease and prospects for epigenetic therapy. Nature 2004; 429: 457-463.
9. Greenblatt SM, Nimer SD. Chromatin modifiers and the promise of epigenetic therapy in acute leukemia. Leukemia 2014; 28: 1396-1406.
10. Wouters BJ, Delwel R. Epigenetics and approaches to targeted epigenetic therapy in acute myeloid leukemia. Blood 2016; 127: 42-52.
11. Baylin SB, Jones PA. A decade of exploring the cancer epigenome-biological and translational implications. Nat Rev Cancer 2011; 11: 726-734.
12. Navada SC, Steinmann J, Lubbert M, Silverman LR. Clinical development of demethylating agents in hematology. J Clin Invest 2014; 124: 40-46.
13. Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH et al. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with430% blasts. Blood 2015; 126: 291-299.
14. Huls G. Azacitidine in AML: a treatment option? Blood 2015; 126: 283-284.
15. Quintas-Cardama A, Santos FP, Garcia-Manero G. Histone deacetylase inhibitors for the treatment of myelodysplastic syndrome and acute myeloid leukemia. Leukemia 2011; 25: 226-235.
16. Kirschbaum M, Gojo I, Goldberg SL, Bredeson C, Kujawski LA, Yang A et al. A phase 1 clinical trial of vorinostat in combination with decitabine in patients with acute myeloid leukaemia or myelodysplastic syndrome. Br J Haematol 2014; 167: 185-193.
17. Garcia-Manero G, Tambaro FP, Bekele NB, Yang H, Ravandi F, Jabbour E et al. Phase II trial of vorinostat with idarubicin and cytarabine for patients with newly diagnosed acute myelogenous leukemia or myelodysplastic syndrome. J Clin Oncol 2012; 30: 2204-2210.
18. Cheung N, So CW. Transcriptional and epigenetic networks in haematological malignancy. FEBS letters 2011; 585: 2100-2111.
19. Labbe RM, Holowatyj A, Yang ZQ. Histone lysine demethylase (KDM) subfamily 4: structures, functions and therapeutic potential. Am J Transl Res 2013; 6: 1-15.
20. Lau PNL, So CW. Polycomb and trithorax factors in transcriptional and epigenetic regulation. In: Huang S, Litt MD, C.A. B (eds). Epigenetic Gene Expression and Regulation. Elsevier: MA, USA, 2015, pp 63-69.
21. Bracken AP, Helin K. Polycomb group proteins: navigators of lineage pathways led astray in cancer. Nat Rev Cancer 2009; 9: 773-784.
22. Ernst T, Chase AJ, Score J, Hidalgo-Curtis CE, Bryant C, Jones AV et al. Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders. Nat Genet 2010; 42: 722-726.
23. Morin RD, Johnson NA, Severson TM, Mungall AJ, An J, Goya R et al. Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin. Nat Genet 2010; 42: 181-185.
24. Muto T, Sashida G, Oshima M, Wendt GR, Mochizuki-Kashio M, Nagata Y et al. Concurrent loss of Ezh2 and Tet2 cooperates in the pathogenesis of myelodysplastic disorders. J Exp Med 2013; 210: 2627-2639.
25. Sashida G, Harada H, Matsui H, Oshima M, Yui M, Harada Y et al. Ezh2 loss promotes development of myelodysplastic syndrome but attenuates its predisposition to leukaemic transformation. Nat Commun 2014; 5: 4177.
26. Mochizuki-Kashio M, Aoyama K, Sashida G, Oshima M, Tomioka T, Muto T et al. Ezh2 loss in hematopoietic stem cells predisposes mice to develop heterogeneous malignancies in an Ezh1-dependent manner. Blood 2015; 126: 1172-1183.
27. Pratcorona M, Abbas S, Sanders MA, Koenders JE, Kavelaars FG, Erpelinck-Verschueren CA et al. Acquired mutations in ASXL1 in acute myeloid leukemia: prevalence and prognostic value. Haematologica 2012; 97: 388-392.
28. Abdel-Wahab O, Adli M, LaFave LM, Gao J, Hricik T, Shih AH et al. ASXL1 mutations promote myeloid transformation through loss of PRC2-mediated gene repression. Cancer Cell 2012; 22: 180-193.
29. Dey A, Seshasayee D, Noubade R, French DM, Liu J, Chaurushiya MS et al. Loss of the tumor suppressor BAP1 causes myeloid transformation. Science 2012; 337: 1541-1546.
30. Sahtoe DD, van Dijk WJ, Ekkebus R, Ovaa H, Sixma TK. BAP1/ASXL1 recruitment and activation for H2A deubiquitination. Nat Commun 2016; 7: 10292.
31. Abdel-Wahab O, Gao J, Adli M, Dey A, Trimarchi T, Chung YR et al. Deletion of Asxl1 results in myelodysplasia and severe developmental defects in vivo. J Exp Med 2013; 210: 2641-2659.
32. Puda A, Milosevic JD, Berg T, Klampfl T, Harutyunyan AS, Gisslinger B et al. Frequent deletions of JARID2 in leukemic transformation of chronic myeloid malignancies. Am J Hematol 2012; 87: 245-250.
33. Meyer C, Hofmann J, Burmeister T, Groger D, Park TS, Emerenciano M et al. The MLL recombinome of acute leukemias in 2013. Leukemia 2013; 27: 2165-2176.
34. Zeisig BB, Cheung N, Yeung J, So CW. Reconstructing the disease model and epigenetic networks for MLL-AF4 leukemia. Cancer Cell 2008; 14: 345-347.
35. Guenther MG, Lawton LN, Rozovskaia T, Frampton GM, Levine SS, Volkert TL et al. Aberrant chromatin at genes encoding stem cell regulators in human mixedlineage leukemia. Genes Dev 2008; 22: 3403-3408.
36. Nguyen AT, Taranova O, He J, Zhang Y. DOT1L the H3K79 methyltransferase, is required for MLL-AF9-mediated leukemogenesis. Blood 2011; 117: 6912-6922.
37. Chang MJ, Wu H, Achille NJ, Reisenauer MR, Chou CW, Zeleznik-Le NJ et al. Histone H3 lysine methyltransferase Dot1 is required for immortalization by MLL oncogenes. Cancer Res 2010; 70: 10234-10242.
38. Bernt KM, Zhu N, Sinha AU, Vempati S, Faber J, Krivtsov AV et al. MLL-rearranged leukemia is dependent on aberrant H3K79 methylation by DOT1L. Cancer Cell 2011; 20: 66-78.
39. Okada Y, Feng Q, Lin Y, Jiang Q, Li Y, Coffield VM et al. hDOT1L links histone methylation to leukemogenesis. Cell 2005; 121: 167-178.
40. Deshpande AJ, Chen L, Fazio M, Sinha AU, Bernt KM, Banka D et al. Leukemic transformation by the MLL-AF6 fusion oncogene requires the H3K79 methyltransferase Dot1l. Blood 2013; 121: 2533-2541.
41. Cheung N, Chan LC, Thompson A, Cleary ML, So CW. Protein arginine-methyltransferase-dependent oncogenesis. Nat Cell Biol 2007; 9: 1208-1215.
42. Cheung N, Fung TK, Zeisig BB, K. H, Rane JK, Mowen KA et al. Targeting aberrant epigenetic networks mediated by PRMT1 and KDM4C in acute myeloid leukemia. Cancer Cell 2016; 29: 32-48.
43. Shia WJ, Okumura AJ, Yan M, Sarkeshik A, Lo MC, Matsuura S et al. PRMT1 interacts with AML1-ETO to promote its transcriptional activation and progenitor cell proliferative potential. Blood 2012; 119: 4953-4962.
44. Neff T, Sinha AU, Kluk MJ, Zhu N, Khattab MH, Stein L et al. Polycomb repressive complex 2 is required for MLL-AF9 leukemia. Proc Natl Acad Sci USA 2012; 109: 5028-5033.
45. Danis E, Yamauchi T, Echanique K, Haladyna J, Kalkur R, Riedel S et al. Inactivation of Eed impedes MLL-AF9-mediated leukemogenesis through Cdkn2a-dependent and Cdkn2a-independent mechanisms in a murine model. Exp Hematol 2015; 43: 930-935.e6.
46. Shi Y, Lan F, Matson C, Mulligan P, Whetstine JR, Cole PA et al. Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell 2004; 119: 941-953.
47. Klose RJ, Kallin EM, Zhang Y. JmjC-domain-containing proteins and histone demethylation. Nat Rev Genet 2006; 7: 715-727.
48. Harris WJ, Huang X, Lynch JT, Spencer GJ, Hitchin JR, Li Y et al. The histone demethylase KDM1A sustains the oncogenic potential of MLL-AF9 leukemia stem cells. Cancer Cell 2012; 21: 473-487.
49. Wong SH, Goode DL, Iwasaki M, Wei MC, Kuo HP, Zhu L et al. The H3K4-methyl epigenome regulates leukemia stem cell oncogenic potential. Cancer Cell 2015; 28: 198-209.
50. Schenk T, Chen WC, Gollner S, Howell L, Jin L, Hebestreit K et al. Inhibition of the LSD1 (KDM1A) demethylase reactivates the all-trans-retinoic acid differentiation pathway in acute myeloid leukemia. Nat Med 2012; 18: 605-611.
51. He J, Nguyen AT, Zhang Y. KDM2b/JHDM1b, an H3K36me2-specific demethylase, is required for initiation and maintenance of acute myeloid leukemia. Blood 2011; 117: 3869-3880.
52. Sroczynska P, Cruickshank VA, Bukowski JP, Miyagi S, Bagger FO, Walfridsson J et al. shRNA screening identifies JMJD1C as being required for leukemia maintenance. Blood 2014; 123: 1870-1882.
53. Chen M, Zhu N, Liu X, Laurent B, Tang Z, Eng R et al. JMJD1C is required for the survival of acute myeloid leukemia by functioning as a coactivator for key transcription factors. Genes Dev 2015; 29: 2123-2139.
54. Zhu N, Chen M, Eng R, DeJong J, Sinha AU, Rahnamay NF et al. MLL-AF9-and HOXA9-mediated acute myeloid leukemia stem cell self-renewal requires JMJD1C. J Clin Invest 2016; 126: 997-1011.
55. Chen CW, Koche RP, Sinha AU, Deshpande AJ, Zhu N, Eng R et al. DOT1L inhibits SIRT1-mediated epigenetic silencing to maintain leukemic gene expression in MLL-rearranged leukemia. Nat Med 2015; 21: 335-343.
56. Agger K, Miyagi S, Pedersen MT, Kooistra SM, Johansen JV, Helin K. Jmjd2/Kdm4 demethylases are required for expression of Il3ra and survival of acute myeloid leukemia cells. Genes Dev 2016; 30: 1278-1288.
57. Arteaga MF, Mikesch JH, Qiu J, Christensen J, Helin K, Kogan SC et al. The histone demethylase PHF8 governs retinoic acid response in acute promyelocytic leukemia. Cancer Cell 2013; 23: 376-389.
58. Fung TK, So CW. Overcoming treatment resistance in acute promyelocytic leukemia and beyond. Oncotarget 2013; 4: 1128-1129.
59. Daigle SR, Olhava EJ, Therkelsen CA, Majer CR, Sneeringer CJ, Song J et al. Selective killing of mixed lineage leukemia cells by a potent small-molecule DOT1L inhibitor. Cancer Cell 2011; 20: 53-65.
60. Daigle SR, Olhava EJ, Therkelsen CA, Basavapathruni A, Jin L, Boriack-Sjodin PA et al. Potent inhibition of DOT1L as treatment of MLL-fusion leukemia. Blood 2013; 122: 1017-1025.
61. Zhou J, Bi C, Cheong LL, Mahara S, Liu SC, Tay KG et al. The histone methyltransferase inhibitor, DZNep, up-regulates TXNIP, increases ROS production, and targets leukemia cells in AML. Blood 2011; 118: 2830-2839.
62. Neff T, Sinha AU, Kluk MJ, Zhu N, Khattab MH, Stein L et al. Polycomb repressive complex 2 is required for MLL-AF9 leukemia. Proc Natl Acad Sci USA 2012; 109: 5028-5033.
63. Xu B, On DM, Ma A, Parton T, Konze KD, Pattenden SG et al. Selective inhibition of EZH2 and EZH1 enzymatic activity by a small molecule suppresses MLL-rearranged leukemia. Blood 2015; 125: 346-357.
64. Knutson SK, Wigle TJ, Warholic NM, Sneeringer CJ, Allain CJ, Klaus CR et al. A selective inhibitor of EZH2 blocks H3K27 methylation and kills mutant lymphoma cells. Nat Chem Biol 2012; 8: 890-896.
65. McCabe MT, Ott HM, Ganji G, Korenchuk S, Thompson C, Van Aller GS et al. EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations. Nature 2012; 492: 108-112.
66. Kim W, Bird GH, Neff T, Guo G, Kerenyi MA, Walensky LD et al. Targeted disruption of the EZH2-EED complex inhibits EZH2-dependent cancer. Nat Chem Biol 2013; 9: 643-650.
67. Gahr M, Schonfeldt-Lecuona C, Kolle MA, Freudenmann RW. Intoxications with the monoamine oxidase inhibitor tranylcypromine: an analysis of fatal and non-fatal events. Eur Neuropsychopharmacol 2013; 23: 1364-1372.
68. Fiskus W, Sharma S, Shah B, Portier BP, Devaraj SG, Liu K et al. Highly effective combination of LSD1 (KDM1A) antagonist and pan-histone deacetylase inhibitor against human AML cells. Leukemia 2014; 28: 2155-2164.
69. Wysocka J, Swigut T, Milne TA, Dou Y, Zhang X, Burlingame AL et al. WDR5 associates with histone H3 methylated at K4 and is essential for H3 K4 methylation and vertebrate development. Cell 2005; 121: 859-872.
70. Ruthenburg AJ, Wang W, Graybosch DM, Li H, Allis CD, Patel DJ et al. Histone H3 recognition and presentation by the WDR5 module of the MLL1 complex. Nat Struct Mol Biol 2006; 13: 704-712.
71. Cao F, Townsend EC, Karatas H, Xu J, Li L, Lee S et al. Targeting MLL1 H3K4 methyltransferase activity in mixed-lineage leukemia. Mol Cell 2014; 53: 247-261.
72. 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: 529-533.
73. 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: 524-528.
74. 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: 538-542.
75. 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: 543-547.