Inhibitors of LSD1 as a potential therapy for acute myeloid leukemia

References

• National Cancer Institute. SEER stat fact sheets: acute myeloid leukemia (AML); 2015 Available from: http://seer.cancer.gov/statfacts/html/amyl.html.
   Google Scholar
• Wang ES. Treating acute myeloid leukemia in older adults. Hematology American Soc Hematol Educ Prog. 2014;2014(1):14–20.
   PubMed Web of Science ®Google Scholar
• Toyota M, Kopecky KJ, Toyota MO, et al. Methylation profiling in acute myeloid leukemia. Blood. 2001;97(9):2823–2829.
   PubMed Web of Science ®Google Scholar
• Shen H, Laird PW. Interplay between the cancer genome and epigenome. Cell. 2013;153(1):38–55.
   PubMed Web of Science ®Google Scholar
• Welch JS, Ley TJ, Link DC, et al. The origin and evolution of mutations in acute myeloid leukemia. Cell. 2012;150(2):264–278.
   PubMed Web of Science ®Google Scholar
• Di Croce L, Raker VA, Corsaro M, et al. Methyltransferase recruitment and DNA hypermethylation of target promoters by an oncogenic transcription factor. Science. 2002;295(5557):1079–1082.
   PubMed Web of Science ®Google Scholar
• Wang J, Hoshino T, Redner RL, et al. ETO, fusion partner in t(8;21) acute myeloid leukemia, represses transcription by interaction with the human N-CoR/mSin3/HDAC1 complex. Proc Natl Acad Sci U S A. 1998;95(18):10860–10865.
   PubMed Web of Science ®Google Scholar
• Heibert SW, Lutterbach B, Durst K, et al. Mechanisms of transcriptional repression by the t(8;21)-, t(12;21)-, and inv(16)-encoded fusion proteins. Cancer Chemother Pharmacol. 2001;48(Suppl 1):S31–4.
   Google Scholar
• Kantarjian HM, Thomas XG, Dmoszynska A, et al. Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol. 2012;30(21):2670–2677.
   PubMed Web of Science ®Google Scholar
• Dombret H, Seymour JF, Butrym A, et al. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015;126(3):291–299.
   PubMed Web of Science ®Google Scholar
• Shi Y, Lan F, Matson C, et al. Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell. 2004;119(7):941–953.
   PubMed Web of Science ®Google Scholar
• Lynch JT, Harris WJ, Somervaille TC. LSD1 inhibition: a therapeutic strategy in cancer? Expert Opin Ther Targets. 2012;16(12):1239–1249.
   PubMed Web of Science ®Google Scholar
• Burg JM, Link JE, Morgan BS, et al. KDM1 class flavin-dependent protein lysine demethylases. Biopolymers. 2015;104(4):213–246.
   PubMed Web of Science ®Google Scholar
• Anand R, Marmorstein R. Structure and mechanism of lysine-specific demethylase enzymes. J Biol Chem. 2007;282(49):35425–35429.
   PubMed Web of Science ®Google Scholar
• Amente S, Lania L, Majello B. The histone LSD1 demethylase in stemness and cancer transcription programs. Biochim Biophys Acta. 2013;1829(10):981–986.
   PubMed Web of Science ®Google Scholar
• Hou H, Yu H. Structural insights into histone lysine demethylation. Curr Opin Struct Biol. 2010;20(6):739–748.
   PubMed Web of Science ®Google Scholar
• Kooistra SM, Helin K. Molecular mechanisms and potential functions of histone demethylases. Nat Rev Mol cell Biol. 2012;13(5):297–31.
   PubMed Web of Science ®Google Scholar
• Shi YJ, Matson C, Lan F, et al. Regulation of LSD1 histone demethylase activity by its associated factors. Mol Cell. 2005;19(6):857–864.
   PubMed Web of Science ®Google Scholar
• Forneris F, Binda C, Dall’Aglio A, et al. A highly specific mechanism of histone H3-K4 recognition by histone demethylase LSD1. J Biol Chem. 2006;281(46):35289–35295.
   PubMed Web of Science ®Google Scholar
• Metzger E, Wissmann M, Yin N, et al. LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription. Nature. 2005;437(7057):436–439.
   PubMed Web of Science ®Google Scholar
• Perillo B, Ombra MN, Bertoni A, et al. DNA oxidation as triggered by H3K9me2 demethylation drives estrogen-induced gene expression. Science. 2008;319(5860):202–206.
   PubMed Web of Science ®Google Scholar
• Nair SS, Nair BC, Cortez V, et al. PELP1 is a reader of histone H3 methylation that facilitates oestrogen receptor-alpha target gene activation by regulating lysine demethylase 1 specificity. EMBO Rep. 2010;11(6):438–444.
   PubMed Web of Science ®Google Scholar
• Biswas D, Milne TA, Basrur V, et al. Function of leukemogenic mixed lineage leukemia 1 (MLL) fusion proteins through distinct partner protein complexes. Proc Natl Acad Sci U S A. 2011;108(38):15751–15756.
   PubMed Web of Science ®Google Scholar
• Nakamura T, Mori T, Tada S, et al. ALL-1 is a histone methyltransferase that assembles a supercomplex of proteins involved in transcriptional regulation. Mol Cell. 2002;10(5):1119–1128.
   PubMed Web of Science ®Google Scholar
• Huang J, Sengupta R, Espejo AB, et al. p53 is regulated by the lysine demethylase LSD1. Nature. 2007;449(7158):105–108.
   PubMed Web of Science ®Google Scholar
• Wang J, Hevi S, Kurash JK, et al. The lysine demethylase LSD1 (KDM1) is required for maintenance of global DNA methylation. Nat Genet. 2009;41(1):125–129.
   PubMed Web of Science ®Google Scholar
• Kahl P, Gullotti L, Heukamp LC, 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):11341–11347.
   PubMed Web of Science ®Google Scholar
• Schulte JH, Lim S, Schramm A, et al. Lysine-specific demethylase 1 is strongly expressed in poorly differentiated neuroblastoma: implications for therapy. Cancer Res. 2009;69(5):2065–2071.
   PubMed Web of Science ®Google Scholar
• Lv T, Yuan D, Miao X, et al. Over-expression of LSD1 promotes proliferation, migration and invasion in non-small cell lung cancer. PLoS One. 2012;7(4):e35065.
   PubMed Web of Science ®Google Scholar
• Lim S, Janzer A, Becker A, 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):512–520.
   PubMed Web of Science ®Google Scholar
• Hayami S, Kelly JD, Cho H-S, et al. Overexpression of LSD1 contributes to human carcinogenesis through chromatin regulation in various cancers. Int J Cancer. 2011;128(3):574–586.
   PubMed Web of Science ®Google Scholar
• Niebel D, Kirfel J, Janzen V, et al. Lysine-specific demethylase 1 (LSD1) in hematopoietic and lymphoid neoplasms. Blood. 2014;124(1):151–152.
   PubMed Web of Science ®Google Scholar
• Sprussel A, Schulte JH, Weber S, et al. Lysine-specific demethylase 1 restricts hematopoietic progenitor proliferation and is essential for terminal differentiation. Leukemia. 2012;26(9):2039–2051.
   PubMed Web of Science ®Google Scholar
• Saleque S, Kim J, Rooke HM, et al. Epigenetic regulation of hematopoietic differentiation by Gfi-1 and Gfi-1b is mediated by the cofactors CoREST and LSD1. Mol Cell. 2007;27(4):562–572.
   PubMed Web of Science ®Google Scholar
• Harris WJ, Huang X, Lynch JT, et al. The histone demethylase KDM1A sustains the oncogenic potential of MLL-AF9 leukemia stem cells. Cancer Cell. 2012;21(4):473–487.
   PubMed Web of Science ®Google Scholar
• Lynch JT, Spencer GJ, Harris WJ, et al. Pharmacological inhibitors of LSD1 promote differentiation of myeloid leukemia cells through a mechanism independent of histone demethylation. 2014.
   Google Scholar
• Mould DP, McGonagle AE, Wiseman DH, et al. Reversible inhibitors of LSD1 as therapeutic agents in acute myeloid leukemia: clinical significance and progress to date. Med Res Rev. 2015;35(3):586–618.
   PubMed Web of Science ®Google Scholar
• Hojfeldt JW, Agger K, Helin K. Histone lysine demethylases as targets for anticancer therapy. Nat Rev Drug Discov. 2013;12(12):917–930.
   PubMed Web of Science ®Google Scholar
• Altucci L, Rossin A, Raffelsberger W, et al. Retinoic acid-induced apoptosis in leukemia cells is mediated by paracrine action of tumor-selective death ligand TRAIL. Nat Med. 2001;7(6):680–686.
   PubMed Web of Science ®Google Scholar
• Glasow A, Prodromou N, Xu K, et al. Retinoids and myelomonocytic growth factors cooperatively activate RARA and induce human myeloid leukemia cell differentiation via MAP kinase pathways. Blood. 2005;105(1):341–349.
   PubMed Web of Science ®Google Scholar
• Yin B, Delwel R, Valk PJ, et al. A retroviral mutagenesis screen reveals strong cooperation between Bcl11a overexpression and loss of the Nf1 tumor suppressor gene. Blood. 2009;113(5):1075–1085.
   PubMed Web of Science ®Google Scholar
• Milojkovic D, Devereux S, Westwood NB, et al. Antiapoptotic microenvironment of acute myeloid leukemia. J Immunol. 2004;173(11):6745–6752.
   PubMed Web of Science ®Google Scholar
• Zuber J, Shi J, Wang E, et al. RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia. Nature. 2011;478(7370):524–528.
   PubMed Web of Science ®Google Scholar
• Huang Y, Greene E, Murray Stewart T, et al. Inhibition of lysine-specific demethylase 1 by polyamine analogues results in reexpression of aberrantly silenced genes. Proc Natl Acad Sci U S A. 2007;104(19):8023–8028.
   PubMed Web of Science ®Google Scholar
• Murray-Stewart T, Woster PM, Casero RA Jr. The re-expression of the epigenetically silenced e-cadherin gene by a polyamine analogue lysine-specific demethylase-1 (LSD1) inhibitor in human acute myeloid leukemia cell lines. Amino Acids. 2014;46(3):585–594.
   PubMed Web of Science ®Google Scholar
• Melki JR, Vincent PC, Clark SJ. Concurrent DNA hypermethylation of multiple genes in acute myeloid leukemia. Cancer Res. 1999;59(15):3730–3740.
   PubMed Web of Science ®Google Scholar
• Melki JR, Vincent PC, Brown RD, et al. Hypermethylation of E-cadherin in leukemia. Blood. 2000;95(10):3208–3213.
   PubMed Web of Science ®Google Scholar
• Lee MG, Wynder C, Schmidt DM, et al. Histone H3 lysine 4 demethylation is a target of nonselective antidepressive medications. Chem Biol. 2006;13(6):563–567.
   PubMed Web of Science ®Google Scholar
• Yang M, Culhane JC, Szewczuk LM, et al. Structural basis for the inhibition of the LSD1 histone demethylase by the antidepressant trans-2-phenylcyclopropylamine. Biochemistry. 2007;46(27):8058–8065.
   PubMed Web of Science ®Google Scholar
• Schmidt DM, McCafferty DG. trans-2-Phenylcyclopropylamine is a mechanism-based inactivator of the histone demethylase LSD1. Biochemistry. 2007;46(14):4408–4416.
   PubMed Web of Science ®Google Scholar
• Schenk T, Chen WC, Gollner S, et al. Inhibition of the LSD1 (KDM1A) demethylase reactivates the all-trans-retinoic acid differentiation pathway in acute myeloid leukemia. Nat Med. 2012;18(4):605–611.
   PubMed Web of Science ®Google Scholar
• Glasow A, Barrett A, Petrie K, et al. DNA methylation-independent loss of RARA gene expression in acute myeloid leukemia. Blood. 2008;111(4):2374–2377.
   PubMed Web of Science ®Google Scholar
• Bernstein BE, Kamal M, Lindblad-Toh K, et al. Genomic maps and comparative analysis of histone modifications in human and mouse. Cell. 2005;120(2):169–181.
   PubMed Web of Science ®Google Scholar
• Howell AL, Stukel TA, Bloomfield CD, et al. Induction of differentiation in blast cells and leukemia colony-forming cells from patients with acute myeloid leukemia. Blood. 1990;75(3):721–729.
   PubMed Web of Science ®Google Scholar
• Corn PG, Smith BD, Ruckdeschel ES, et al. E-cadherin expression is silenced by 5’ CpG island methylation in acute leukemia. Clin Cancer Res. 2000;6(11):4243–4248.
   PubMed Web of Science ®Google Scholar
• Sankar S, Bell R, Stephens B, et al. Mechanism and relevance of EWS/FLI-mediated transcriptional repression in Ewing sarcoma. Oncogene. 2013;32(42):5089–5100.
   PubMed Web of Science ®Google Scholar
• Fiskus W, Sharma S, Shah B, et al. Highly effective combination of LSD1 (KDM1A) antagonist and pan-histone deacetylase inhibitor against human AML cells. Leukemia. 2014;28(11):2155–2164.
   PubMed Web of Science ®Google Scholar
• Balusu R, Fiskus W, Rao R, et al. Targeting levels or oligomerization of nucleophosmin 1 induces differentiation and loss of survival of human AML cells with mutant NPM1. Blood. 2011;118(11):3096–3106.
   PubMed Web of Science ®Google Scholar
• Maes T, Tirapu I, Mascaro C, et al. Preclinical characterization of a potent and selective inhibitor of the histone demethylase KDM1A for MLL leukemia. J Clin Oncol 2013;31:abstract e13543.
   Web of Science ®Google Scholar
• Zheng YC, Yu B, Jiang GZ, et al. Irreversible LSD1 inhibitors: application of tranylcypromine and its derivatives in cancer treatment. Curr Top Med Chem. 2016 Feb 16. [Epub ahead of print]
   PubMedGoogle Scholar
• Smitheman K, Cusan M, Yan L, et al. Inhibition of LSD1 for the treatment of cancer. Cancer Res 2015;75(15 Suppl):abstract 3513.
   Google Scholar
• Swords R, Perez A, Rodriguez A, et al. The small molecula IMG-98, a potent and selective inhibitor of the lysine demehtylast LSD-1, effectively augments the pro-differentiation effects of ATRA in a preclinical model of AML. Am Soc Hematol Ann Meet. Dec 7 2015;126(23): abstract 460.
   Google Scholar
• Kleppe M, Shank K, Efthymia P, et al. Lysine-specific histone demethylase, LSD1, (KDM1A) as a novel therapeutic target in myeloproliferative neoplasms. Am Soc Hematol Ann Meet. Dec 7 2015;126(23): abstract 601.
   Google Scholar
• Metzeler KH, Walker A, Geyer S, et al. DNMT3A mutations and response to the hypomethylating agent decitabine in acute myeloid leukemia. Leukemia. 2012;26(5):1106–1107.
   PubMed Web of Science ®Google Scholar
• Emadi A, Faramand R, Carter-Cooper B, et al. Presence of isocitrate dehydrogenase mutations may predict clinical response to hypomethylating agents in patients with acute myeloid leukemia. Am J Hematol. 2015;90(5):E77–9.
   PubMed Web of Science ®Google Scholar
• Itzykson R, Kosmider O, Cluzeau T, et al. Impact of TET2 mutations on response rate to azacitidine in myelodysplastic syndromes and low blast count acute myeloid leukemias. Leukemia. 2011;25(7):1147–1152.
   PubMed Web of Science ®Google Scholar
• McGrath JP, Williamson KE, Balasubramanian S, et al. Pharmacological inhibition of the histone lysine demethylase KDM1A suppresses the growth of multiple acute myeloid leukemia subtypes. Cancer Res. 2016;76:1975–1988.
   PubMed Web of Science ®Google Scholar
• Juliusson G, Antunovic P, Derolf A, et al. Age and acute myeloid leukemia: real world data on decision to treat and outcomes from the Swedish acute leukemia registry. Blood. 2009;113(18):4179–4187.
   PubMed Web of Science ®Google Scholar
• Quintas-Cardama A, Ravandi F, Liu-Dumlao T, et al. Epigenetic therapy is associated with similar survival compared with intensive chemotherapy in older patients with newly diagnosed acute myeloid leukemia. Blood. 2012;120(24):4840–4845.
   PubMed Web of Science ®Google Scholar
• Gupta N, Miller A, Gandhi S, et al. Comparison of epigenetic versus standard induction chemotherapy for newly diagnosed acute myeloid leukemia patients >/=60 years old. Am J Hematol. 2015;90(7):639–646.
   PubMed Web of Science ®Google Scholar
• Han H, Yang X, Pandiyan K, et al. Synergistic re-activation of epigenetically silenced genes by combinatorial inhibition of DNMTs and LSD1 in cancer cells. PLoS One. 2013;8(9):e75136.
   PubMed Web of Science ®Google Scholar
• Fredly H, Gjertsen BT, Bruserud O. Histone deacetylase inhibition in the treatment of acute myeloid leukemia: the effects of valproic acid on leukemic cells, and the clinical and experimental evidence for combining valproic acid with other antileukemic agents. Clin Epigenetics. 2013;5(1):12.
   PubMed Web of Science ®Google Scholar
• Ocio EM, Herrera P, Olave MT, et al. Panobinostat as part of induction and maintenance for elderly patients with newly diagnosed acute myeloid leukemia: phase Ib/II panobidara study. Haematologica. 2015;100(10):1294–1300.
   PubMed Web of Science ®Google Scholar
• Fredly H, Ersvaer E, Kittang AO, et al. The combination of valproic acid, all-trans retinoic acid and low-dose cytarabine as disease-stabilizing treatment in acute myeloid leukemia. Clin Epigenetics. 2013;5(1):13.
   PubMed Web of Science ®Google Scholar
• Leitch C, Osdal T, Andresen V, et al. Hydroxyurea synergizes with valproic acid in wild-type p53 acute myeloid leukaemia. Oncotarget. 2016 Feb 16;7(7):8105–8118.
   PubMed Web of Science ®Google Scholar
• Mohammad HP, Smitheman KN, Kamat CD, et al. A DNA hypomethylation signature predicts antitumor activity of LSD1 inhibitors in SCLC. Cancer Cell. 2015;28(1):57–69..
   PubMed Web of Science ®Google Scholar