Pharmacological inhibition of LSD1 for the treatment of MLL-rearranged leukemia

Journal of Hematology and Oncology

Volumn 9, Issue 1, 2016, Pages

  Feng, Zizhen ^a   Yao, Yuan ^a   Zhou, Chao ^a   Chen, Fengju ^a   Wu, Fangrui ^a   Wei, Liping ^a   Liu, Wei ^a,b   Dong, Shuo ^a   Redell, Michele ^a,b   Mo, Qianxing ^a   Song, Yongcheng ^a  

^a BAYLOR COLLEGE OF MEDICINE   (United States)

^b Texas Children's Cancer and Hematology Centers   (United States)

Author keywords

Drug discovery; Enzyme inhibitor; Leukemia therapeutics; Lysine specific demethylase 1; MLL rearranged leukemia

Indexed keywords

ANTILEUKEMIC AGENT; HISTONE H3; HISTONE H3K4; HISTONE LYSINE METHYLTRANSFERASE INHIBITOR; HISTONE METHYLTRANSFERASE; HISTONE METHYLTRANSFERASE DOT1L; LYSINE SPECIFIC DEMETHYLASE 1; LYSINE SPECIFIC DEMETHYLASE 1 INHIBITOR; MIXED LINEAGE LEUKEMIA PROTEIN; SYC 522; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR HOXA9; TRANSCRIPTION FACTOR MEIS1; UNCLASSIFIED DRUG; DOT1L PROTEIN, HUMAN; ENZYME INHIBITOR; HISTONE; HISTONE DEMETHYLASE; HISTONE LYSINE METHYLTRANSFERASE; KDM1A PROTEIN, HUMAN; LYSINE; METHYLTRANSFERASE; MLL PROTEIN, HUMAN; MONOAMINE OXIDASE INHIBITOR;

ACUTE LEUKEMIA; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; ARTICLE; CANCER SURVIVAL; CELL DIFFERENTIATION; CELL MIGRATION; CELL PROLIFERATION; CELL VIABILITY; CONTROLLED STUDY; CYTOTOXICITY; DOWN REGULATION; DRUG EFFICACY; DRUG HALF LIFE; DRUG POTENCY; DRUG POTENTIATION; DRUG TARGETING; EC50; ENZYME INHIBITION; GENE EXPRESSION REGULATION; GENE REARRANGEMENT; HISTONE METHYLATION; HUMAN; HUMAN CELL; IC50; IN VITRO STUDY; IN VIVO STUDY; MLL GENE; NONHUMAN; PROTEIN DEPLETION; PROTEIN EXPRESSION; STEM CELL SELF-RENEWAL; SURVIVAL TIME; UPREGULATION; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMICAL STRUCTURE; CHEMISTRY; CHILD; DRUG EFFECTS; DRUG SCREENING; GENETICS; LEUKEMIA; MCF-7 CELL LINE; METABOLISM; METHYLATION; NONOBESE DIABETIC MOUSE; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SCID MOUSE; TUMOR CELL LINE; U-937 CELL LINE; WESTERN BLOTTING;

ANIMALS; BLOTTING, WESTERN; CELL LINE, TUMOR; CELL PROLIFERATION; CHILD; DRUG SYNERGISM; ENZYME INHIBITORS; GENE EXPRESSION REGULATION, LEUKEMIC; GENE REARRANGEMENT; HISTONE DEMETHYLASES; HISTONE-LYSINE N-METHYLTRANSFERASE; HISTONES; HUMANS; LEUKEMIA; LYSINE; MCF-7 CELLS; METHYLATION; METHYLTRANSFERASES; MICE, INBRED NOD; MICE, SCID; MOLECULAR STRUCTURE; MONOAMINE OXIDASE INHIBITORS; MYELOID-LYMPHOID LEUKEMIA PROTEIN; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; U937 CELLS; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84960481338     PISSN: None     EISSN: 17568722     Source Type: Journal    
DOI: 10.1186/s13045-016-0252-7     Document Type: Article

References (50)

1. Leukemia Lymphoma Society database. http://www.lls.org/#/diseaseinformation/leukemia/. Accessed 18 Sept 2015.
2. Laszlo GS, Alonzo TA, Gudgeon CJ, Harrington KH, Kentsis A, Gerbing RB, et al. High expression of myocyte enhancer factor 2C (MEF2C) is associated with adverse-risk features and poor outcome in pediatric acute myeloid leukemia: A report from the Children's Oncology Group. J Hematol Oncol. 2015;8(1):115.
3. Chen CS, Sorensen PH, Domer PH, Reaman GH, Korsmeyer SJ, Heerema NA, et al. Molecular rearrangements on chromosome 11q23 predominate in infant acute lymphoblastic leukemia and are associated with specific biologic variables and poor outcome. Blood. 1993;81(9):2386-93.
4. Hilden JM, Dinndorf PA, Meerbaum SO, Sather H, Villaluna D, Heerema NA, et al. Analysis of prognostic factors of acute lymphoblastic leukemia in infants: Report on CCG 1953 from the Children's Oncology Group. Blood. 2006;108(2):441-51.
5. Mrozek K, Heinonen K, Lawrence D, Carroll AJ, Koduru PR, Rao KW, et al. Adult patients with de novo acute myeloid leukemia and t(9; 11)(p22; q23) have a superior outcome to patients with other translocations involving band 11q23: A cancer and leukemia group B study. Blood. 1997;90(11):4532-8.
6. Krivtsov AV, Armstrong SA. MLL translocations, histone modifications and leukaemia stem-cell development. Nat Rev. 2007;7(11):823-33.
7. Briggs SD, Bryk M, Strahl BD, Cheung WL, Davie JK, Dent SY, et al. Histone H3 lysine 4 methylation is mediated by Set1 and required for cell growth and rDNA silencing in Saccharomyces cerevisiae. Genes Dev. 2001;15(24):3286-95.
8. Milne TA, Briggs SD, Brock HW, Martin ME, Gibbs D, Allis CD, et al. MLL targets SET domain methyltransferase activity to Hox gene promoters. Mol Cell. 2002;10(5):1107-17.
9. Okada Y, Feng Q, Lin Y, Jiang Q, Li Y, Coffield VM, et al. hDOT1L links histone methylation to leukemogenesis. Cell. 2005;121(2):167-78.
10. Nakamura T, Mori T, Tada S, Krajewski W, Rozovskaia T, Wassell R, et al. ALL-1 is a histone methyltransferase that assembles a supercomplex of proteins involved in transcriptional regulation. Mol Cell. 2002;10(5):1119-28.
11. 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(7):941-53.
12. Daser A, Rabbitts TH. The versatile mixed lineage leukaemia gene MLL and its many associations in leukaemogenesis. Semin Cancer Biol. 2005;15(3):175-88.
13. Bitoun E, Oliver PL, Davies KE. The mixed-lineage leukemia fusion partner AF4 stimulates RNA polymerase II transcriptional elongation and mediates coordinated chromatin remodeling. Hum Mol Genet. 2007;16(1):92-106.
14. Krivtsov AV, Feng Z, Lemieux ME, Faber J, Vempati S, Sinha AU, et al. H3K79 methylation profiles define murine and human MLL-AF4 leukemias. Cancer Cell. 2008;14(5):355-68.
15. Yao Y, Chen P, Diao J, Cheng G, Deng L, Anglin JL, et al. Selective inhibitors of histone methyltransferase DOT1L: Design, synthesis, and crystallographic studies. J Am Chem Soc. 2011;133(42):16746-9.
16. Anglin JL, Deng L, Yao Y, Cai G, Liu Z, Jiang H, et al. Synthesis and structure-activity relationship investigation of adenosine-containing inhibitors of histone methyltransferase DOT1L. J Med Chem. 2012;55(18):8066-74.
17. Deng L, Zhang L, Yao Y, Wang C, Redell MS, Dong S, et al. Synthesis, activity and metabolic stability of non-ribose containing inhibitors of histone methyltransferase DOT1L. Med Chem Comm. 2013;4(5):822-6.
18. 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(1):53-65.
19. Basavapathruni A, Jin L, Daigle SR, Majer CR, Therkelsen CA, Wigle TJ, et al. Conformational adaptation drives potent, selective and durable inhibition of the human protein methyltransferase DOT1L. Chem Biol Drug Des. 2012;80(6):971-80.
20. 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(6):1017-25.
21. Yu W, Chory EJ, Wernimont AK, Tempel W, Scopton A, Federation A, et al. Catalytic site remodelling of the DOT1L methyltransferase by selective inhibitors. Nat Commun. 2012;3:1288.
22. Binda C, Valente S, Romanenghi M, Pilotto S, Cirilli R, Karytinos A, et al. Biochemical, structural, and biological evaluation of tranylcypromine derivatives as inhibitors of histone demethylases LSD1 and LSD2. J Am Chem Soc. 2010;132(19):6827-33.
23. Kerenyi MA, Shao Z, Hsu YJ, Guo G, Luc S, O'Brien K, et al. Histone demethylase Lsd1 represses hematopoietic stem and progenitor cell signatures during blood cell maturation. eLife. 2013;2:e00633.
24. Kahl P, Gullotti L, Heukamp LC, Wolf S, Friedrichs N, Vorreuther R, et al. Androgen receptor coactivators lysine-specific histone demethylase 1 and four and a half LIM domain protein 2 predict risk of prostate cancer recurrence. Cancer Res. 2006;66(23):11341-7.
25. Lim S, Janzer A, Becker A, Zimmer A, Schule R, Buettner R, et al. Lysine-specific demethylase 1 (LSD1) is highly expressed in ER-negative breast cancers and a biomarker predicting aggressive biology. Carcinogenesis. 2010;31(3):512-20.
26. Schulte JH, Lim S, Schramm A, Friedrichs N, Koster J, Versteeg R, et al. Lysine-specific demethylase 1 is strongly expressed in poorly differentiated neuroblastoma: Implications for therapy. Cancer Res. 2009;69(5):2065-71.
27. 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(4):473-87.
28. Dent SY, Chandra J. The lasting influence of LSD1 in the blood. eLife. 2013;2:e00963.
29. Lynch JT, Harris WJ, Somervaille TC. LSD1 inhibition: A therapeutic strategy in cancer? Expert Opin Ther Targets. 2012;16(12):1239-49.
30. Neelamegam R, Ricq EL, Malvaez M, Patnaik D, Norton S, Carlin SM, et al. Brain-penetrant LSD1 inhibitors can block memory consolidation. ACS Chem Neurosci. 2012;3(2):120-8.
31. Sorna V, Theisen ER, Stephens B, Warner SL, Bearss DJ, Vankayalapati H, et al. High-throughput virtual screening identifies novel N'-(1-phenylethylidene)-benzohydrazides as potent, specific, and reversible LSD1 inhibitors. J Med Chem. 2013;56(23):9496-508.
32. Suzuki T, Miyata N. Lysine demethylases inhibitors. J Med Chem. 2011;54(24):8236-50.
33. Zheng YC, Duan YC, Ma JL, Xu RM, Zi X, Lv WL, et al. Triazole-dithiocarbamate based selective lysine specific demethylase 1 (LSD1) inactivators inhibit gastric cancer cell growth, invasion, and migration. J Med Chem. 2013;56(21):8543-60.
34. 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(11):2155-64.
35. Prusevich P, Kalin JH, Ming SA, Basso M, Givens J, Li X, et al. A selective phenelzine analogue inhibitor of histone demethylase LSD1. ACS Chem Biol. 2014;9(6):1284-93.
36. Huang Y, Greene E, Murray Stewart T, Goodwin AC, Baylin SB, Woster PM, et al. Inhibition of lysine-specific demethylase 1 by polyamine analogues results in reexpression of aberrantly silenced genes. Proc Natl Acad Sci USA. 2007;104(19):8023-8.
37. Sharma SK, Wu Y, Steinbergs N, Crowley ML, Hanson AS, Casero RA, et al. (Bis)urea and (bis)thiourea inhibitors of lysine-specific demethylase 1 as epigenetic modulators. J Med Chem. 2010;53(14):5197-212.
38. Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J, et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature. 1994;367(6464):645-8.
39. Misaghian N, Ligresti G, Steelman LS, Bertrand FE, Basecke J, Libra M, et al. Targeting the leukemic stem cell: The Holy Grail of leukemia therapy. Leukemia. 2009;23(1):25-42.
40. Liu W, Deng L, Song Y, Redell M. DOT1L inhibition sensitizes MLL-rearranged AML to chemotherapy. PLoS One. 2014;9(5):e98270.
41. Chou TC. Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev. 2006;58(3):621-81.
42. Ross ME, Mahfouz R, Onciu M, Liu H-C, Zhou X, Song G, et al. Gene expression profiling of pediatric acute myelogenous leukemia. Blood. 2004;104(12):3679-87.
43. Smith AD, Roda D, Yap TA. Strategies for modern biomarker and drug development in oncology. J Hematol Oncol. 2014;7:70.
44. Thiel AT, Blessington P, Zou T, Feather D, Wu X, Yan J, et al. MLL-AF9-induced leukemogenesis requires coexpression of the wild-type Mll allele. Cancer Cell. 2010;17(2):148-59.
45. Wang W, Tang G, Cortes JE, Liu H, Ai D, Yin CC, et al. Chromosomal rearrangement involving 11q23 locus in chronic myelogenous leukemia: A rare phenomenon frequently associated with disease progression and poor prognosis. J Hematol Oncol. 2015;8:32.
46. Metzger E, Wissmann M, Yin N, Muller JM, Schneider R, Peters AH, et al. LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription. Nature. 2005;437(7057):436-9.
47. Wang J, Hevi S, Kurash JK, Lei H, Gay F, Bajko J, et al. The lysine demethylase LSD1 (KDM1) is required for maintenance of global DNA methylation. Nat Genet. 2009;41(1):125-9.
48. Sprussel A, Schulte JH, Weber S, Necke M, Handschke K, Thor T, et al. Lysine-specific demethylase 1 restricts hematopoietic progenitor proliferation and is essential for terminal differentiation. Leukemia. 2012;26(9):2039-51.
49. Jiang X, Sun L, Qiu JJ, Sun X, Li S, Wang X, et al. A novel application of furazolidone: Anti-leukemic activity in acute myeloid leukemia. PLoS One. 2013;8(8):e72335.
50. Zeisig BB, Kwok C, Zelent A, Shankaranarayanan P, Gronemeyer H, Dong S, et al. Recruitment of RXR by homotetrameric RARalpha fusion proteins is essential for transformation. Cancer Cell. 2007;12(1):36-51.