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Drug Evaluation

Panobinostat for the treatment of acute myelogenous leukemia

, , , , , , , , & show all
Pages 1117-1131 | Received 15 Feb 2016, Accepted 21 Jul 2016, Published online: 08 Aug 2016

References

  • Döhner H, Estey EH, Amadori S, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European Leukemia Net. Blood. 2010;115:453–474.
  • 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;113:4179–4187.
  • Papaemmanuil E, Gerstung M, Bullinger L, et al. Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med. 2016;374:2209–2221.
  • Döhner H, Weisdorf DJ, Bloomfield CD. Acute myeloid leukemia. N Engl J Med. 2015;373:1136–1152.
  • Ravandi F, Ritchie E, Sayar H, et al. Improved survival in patients with first re- lapsed or refractory acute myeloid leukemia (AML) treated with vosaroxin plus cytarabine versus placebo plus cytarabine: results of a phase 3 double-blind randomized controlled multinational study (VALOR). Blood. 2014;124:Abstract LBA6.
  • Gasiorowski RE, Clark GJ, Bradstock K, et al. Antibody therapy for acute myeloid leukaemia. Br J Haematol. 2014;164:481–495.
  • Dawson MA, Kouzarides T, Huntly BJP. Targeting epigenetic readers in cancer. N Engl J Med. 2012;367:647–657.
  • Abdel-Wahab O, Levine RL. Mutations in epigenetic modifiers in the pathogenesis and therapy of acute myeloid leukemia. Blood. 2013;121:3563–3572.
  • Vigna E, Recchia AG, Madeo A, et al. Epigenetic regulation in myelodysplastic syndromes: implications for therapy. Expert Opin Investig Drugs. 2011;20:465–493.
  • Wang F, Travins J, De LaBarre B, et al. Targeted inhibition of mutant IDH2 in leukemia cells induces cellular differentiation. Science. 2013;340:622–626.
  • Stahl M, Gore SD, Vey N, et al. Lost in translation? Ten years of development of histone deacetylase inhibitors in acute myeloid leukemia and myelodysplastic syndromes. Expert Opin Investig Drugs. 2016;25:307–317.
  • Choudhary C, Kumar C, Gnad F, et al. Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009;325:834–840.
  • Bolden JE, Peart MJ, Johnstone RW. Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discov. 2006;5:769–784.
  • Minucci S, Pelicci PG. Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer. Nat Rev Cancer. 2006;6:38–51.
  • Gu W, Roeder RG. Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain. Cell. 1997;90:595–606.
  • Qian DZ, Kachhap SK, Collis SJ, et al. Class II histone deacetylases are associated with VHL-independent regulation of hypoxia- inducible factor 1 alpha. Cancer Res. 2006;66:8814–8821.
  • Qian DZ, Kato Y, Shabbeer S, et al. Targeting tumor angiogenesis with histone deacetylase inhibitors: the hydroxamic acid derivative LBH589. Clin Cancer Res. 2006;12:634–642.
  • Yang Y, Rao R, Shen J, et al. Role of acetylation and extracellular location of heat shock protein 90alpha in tumor cell invasion. Cancer Res. 2008;68:4833–4842.
  • Bali P, Pranpat M, Bradner J, et al. Inhibition of histone deacetylase 6 acetylates and disrupts the chaperone function of heat shock protein 90: a novel basis for antileukemia activity of histone deacetylase inhibitors. J Biol Chem. 2005;280:26729–26734.
  • Bishton MJ, Johnstone RW, Dickinson M, et al. Overview of histone deacetylase inhibitors in haematological malignancies. Pharmaceuticals. 2010;3:2674–2688.
  • Verheul HM, Salumbides B, Van Erp K, et al. Combination strategy targeting the hypoxia inducible factor-1 alpha with mammalian target of rapamycin and histone deacetylase inhibitors. Clin Cancer Res. 2008;14:3589–3597.
  • Atadja P. Development of the pan-DAC inhibitor panobinostat (LBH589): successes and challenges. Cancer Lett. 2009;280:233–241.
  • Wahaib K, Beggs AE, Campbell H, et al. Panobinostat: a histone deacetylase inhibitor for the treatment of relapsed or refractory multiple myeloma. Am J Health Syst Pharm. 2016;73:441–450.
  • Greig SL. Panobinostat: a review in relapsed or refractory multiple myeloma. Target Oncol. 2016;11:107–114.
  • Richardson PG, Hungria VT, Yoon SS, et al. Panobinostat plus bortezomib and dexamethasone in previously treated multiple myeloma: outcomes by prior treatment. Blood. 2016;127:713–721.
  • Egger G, Liang G, Aparicio A, et al. Epigenetics in human disease and prospects for epigenetic therapy. Nature. 2004;429:457–463.
  • Fong CY, Morison J, Dawson MA. Epigenetics in the hematologic malignancies. Haematologica. 2014;99:1772–1783.
  • Greenblatt SM, Nimer SD. Chromatin modifiers and the promise of epigenetic therapy in acute leukemia. Leukemia. 2014;28:1396–1406.
  • Figueroa ME, Lugthart S, Li Y, et al. DNA methylation signatures identify biologically distinct subtypes in acute myeloid leukemia. Cancer Cell. 2010;17:13–27.
  • Gröschel S, Sanders MA, Hoogenboezem R, et al. A single oncogenic enhancer rearrangement causes concomitant EVI1 and GATA2 deregulation in leukemia. Cell. 2014;157:369–381.
  • Esteller M. Epigenetics in cancer. N Engl J Med. 2008;358:1148–1159.
  • Jin B, Li Y, Robertson KD. DNA methylation: superior or subordinate in the epigenetic hierarchy? Esteller M, editor. Genes and Cancer. 2011;2:607–617.
  • Feinberg AP, Ohlsson R, Henikoff S. The epigenetic progenitor origin of human cancer. Nat Rev Genet. 2006;7:21–33.
  • Gopalakrishnan S, Van Emburgh BO, Robertson KD. DNA methylation in development and human disease. Mutat Res. 2008;647:30–38.
  • Baylin SB, Jones PA. A decade of exploring the cancer epigenome - biological and translational implications. Nat Rev Cancer. 2011;11:726–734.
  • Guillamot M, Cimmino L, Aifantis I. The impact of DNA methylation in hematopoietic malignancies. Trends Cancer. 2016;2:70–83.
  • Wouters BJ, Delwel R. Epigenetics and approaches to targeted epigenetic therapy in acute myeloid leukemia. Blood. 2016;127:42–52.
  • Delcuve GP, Khan DH, Davie JR. Roles of histone deacetylases in epigenetic regulation: emerging paradigms from studies with inhibitors. Clin Epigenetics. 2012;4:5.
  • Verdin E, Ott M. 50 years of protein acetylation: from gene regulation to epigenetics, metabolism and beyond. Nat Rev Mol Cell Biol. 2015;16:258–264.
  • Bose P, Grant S. Rational combinations of targeted agents in AML. J Clin Med. 2015;4:634–664.
  • Dokmanovic M, Clarke C, Marks PA. Histone deacetylase inhibitors: overview and perspectives. Mol Cancer Res. 2007;5:981–989.
  • Witt O, Deubzer HE, Milde T, et al. HDAC family: what are the cancer relevant targets? Cancer Lett. 2009;277:8–21.
  • Scott GK, Mattie MD, Berger CE, et al. Rapid alteration of microRNA levels by histone deacetylase inhibition. Cancer Res. 2006;66:1277–1281.
  • Gregoretti IV, Lee YM, Goodson HV. Molecular evolution of the histone deacetylase family: functional implications of phylogenetic analysis. J Mol Biol. 2004;338:17–31.
  • Ropero S, Esteller M. The role of histone deacetylases (HDACs) in human cancer. Mol Oncol. 2007;1:19–25.
  • Marks PA, Xu WS. Histone deacetylase inhibitors: potential in cancer therapy. J Cell Biochem. 2009;107:600–608.
  • Rodriguez-Gonzalez A, Lin T, Ikeda AK, et al. Role of the aggresome pathway in cancer: targeting histone deacetylase 6-dependent protein degradation. Cancer Res. 2008;68:2557–2560.
  • Smith KT, Workman JL. Histone deacetylase inhibitors: anticancer compounds. Int J Biochem Cell Biol. 2009;41:21–25.
  • Prince HM, Bishton M. Panobinostat (LBH589): a novel pandeacetylase inhibitor with activity in T cell lymphoma. Hematol Meet Rep. 2009;3:33–38.
  • Fredly H, Gjertsen BT, Bruserud Ø. 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;5:12.
  • Shao W, Growney JD, Feng Y, et al. Potent anticancer activity of the pan-deacetylase inhibitor panobinostat (LBH589) as a single agent in in vitro and in vivo tumor models [Abstract 6244]. In: 99th American Association of Cancer Research Annual Meeting; 2008 Apr 12–16; San Diego (CA).
  • Xu WS, Parmigiani RB, Marks PA. Histone deacetylase inhibitors: molecular mechanisms of action. Oncogene. 2007;26:5541–5552.
  • Tan P, Wei A, Mithraprabhu S, et al. Dual epigenetic targeting with panobinostat and azacitidine in acute myeloid leukemia and high-risk myelodysplastic syndrome. Blood Cancer J. 2014 Jan;4(1):e170.
  • Novotny-Diermayr V, Sausgruber N, Loh YK, et al. Pharmacodynamic evaluation of the target efficacy of SB939, an oral HDAC inhibitor with selectivity for tumor tissue. Mol Cancer Ther. 2011;10:1207–1217.
  • Bots M, Verbrugge I, Martin BP, et al. Differentiation therapy for the treatment of t(8;21) acute myeloid leukemia using histone deacetylase inhibitors. Blood. 2014;123:1341–1352.
  • Minucci S, Nervi C, Lo Coco F, et al. Histone deacetylases: a common molecular target for differentiation treatment of acute myeloid leukemias? Oncogene. 2001;20:3110–3115.
  • Rosato R, Hock S, Dent P, et al. LBH-589 (panobinostat) potentiates fludarabine anti-leukemic activity through a JNK- and XIAP-dependent mechanism. Leuk Res. 2012;36:491–498.
  • Xie C, Drenberg C, Edwards H, et al. Panobinostat enhances cytarabine and daunorubicin sensitivities in AML cells through suppressing the expression of BRCA1, CHK1, and Rad51. PLoS One. 2013;8:e79106.
  • 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;28:2155–2164.
  • Reikvam H, Ersvaer E, Bruserud O. Heat shock protein 90 - a potential target in the treatment of human acute myelogenous leukemia. Curr Cancer Drug Targets. 2009;9(6):761–776.
  • Ha K, Fiskus W, Choi DS, et al. Histone deacetylase inhibitor treatment induces ‘BRCAness’ and synergistic lethality with PARP inhibitor and cisplatin against human triple negative breast cancer cells. Oncotarget. 2014;5:5637–5650.
  • Joshi AD, Barabutis N, Birmpas C, et al. Histone deacetylase inhibitors prevent pulmonary endothelial hyperpermeability and acute lung injury by regulating heat shock protein 90 function. Am J Physiol Lung Cell Mol Physiol. 2015;309:L1410–L1419.
  • Zou H, Wu Y, Navre M, et al. Characterization of the two catalytic domains in histone deacetylase 6. Biochem Biophys Res Commun. 2006;341:45–50.
  • Fiskus W, Rao R, Fernandez P, et al. Molecular and biologic characterization and drug sensitivity of pan-histone deacetylase inhibitor-resistant acute myeloid leukemia cells. Blood. 2008;112:2896–2905.
  • George P, Bali P, Annavarapu S, et al. Combination of the histone deacetylase inhibitor LBH589 and the hsp90 inhibitor 17-AAG is highly active against human CML-BC cells and AML cells with activating mutation of FLT-3. Blood. 2005;105:1768–1776.
  • Reikvam H, Brenner AK, Nepstad I, et al. Heat shock protein 70 -the next chaperone to target in the treatment of human acute myelogenous leukemia? Expert Opin Ther Targets. 2014;18:929–944.
  • Daugaard M, Rohde M, Jäättelä M. The heat shock protein 70 family: highly homologous proteins with overlapping and distinct functions. FEBS Lett. 2007;581(19):3702–3710.
  • Kampinga HH, Craig EA. The HSP70 chaperone machinery: J proteins as drivers of functional specificity. Nat Rev Mol Cell Biol. 2010;11(8):579–592.
  • Frydman J, Höhfeld J. Chaperones get in touch: the Hip-Hop connection. Trends Biochem Sci. 1997;22(3):87–92.
  • Guo F, Rocha K, Bali P, et al. Abrogation of heat shock protein 70 induction as a strategy to increase antileukemia activity of heat shock protein 90 inhibitor 17-allylamino-demethoxy geldanamycin. Cancer Res. 2005;65:10536–10544.
  • Powers MV, Clarke PA, Workman P. Dual targeting of HSC70 and HSP72 inhibits HSP90 function and induces tumor-specific apoptosis. Cancer Cell. 2008;14(3):250–262.
  • Massey AJ, Williamson DS, Browne H, et al. A novel, small molecule inhibitor of Hsc70/Hsp70 potentiates
Hsp90 inhibitor induced apoptosis in HCT116 colon carcinoma cells. Cancer Chemother Pharmacol. 2010;66(3):535–545.
  • Powers MV, Jones K, Barillari C, et al. Targeting HSP70: the second potentially druggable heat shock protein and molecular chaperone? Cell Cycle. 2010;9:1542–1550.
  • Evans CG, Chang L, Gestwicki JE. Heat shock protein 70 (hsp70) as an emerging drug target. J Med Chem. 2010;53(12):4585–4602.
  • Schlecht R, Scholz SR, Dahmen H, et al. Functional analysis of hsp70 inhibitors. PLoS One. 2013;8:e78443.
  • Kaiser M, Kühnl A, Reins J, et al. Antileukemic activity of the HSP70 inhibitor pifithrin-μ in acute leukemia. Blood Cancer J. 2011;7:e28.
  • Reikvam H, Hatfield KJ, Ersvaer E, et al. Expression profile of heat shock proteins in acute myeloid leukaemia patients reveals a distinct signature strongly associated with FLT3 mutation status - consequences and potentials for pharmacological intervention. Br J Haematol. 2012;156:468–480.
  • Reikvam H, Nepstad I, Sulen A, et al. Increased antileukemic effects in human acute myeloid leukemia by combining HSP70 and HSP90 inhibitors. Expert Opin Investig Drugs. 2013;22:551–563.
  • Al Shaer L, Walsby E, Gilkes A, et al. Heat shock protein 90 inhibition is cytotoxic to primary AML cells expressing mutant FLT3 and results in altered downstream signalling. Br J Haematol. 2008;141:483–493.
  • Jantunen E, Varmavuo V. Plerixafor for mobilization of blood stem cells in autologous transplantation: an update. Expert Opin Biol Ther. 2014;14:851–861.
  • Ayala F, Dewar R, Kieran M, et al. Contribution of bone microenvironment to leukemogenesis and leukemia progression. Leukemia. 2009;23:2233–2241.
  • Mandawat A, Fiskus W, Buckley KM, et al. Pan-histone deacetylase inhibitor panobinostat depletes CXCR4 levels and signaling and exerts synergistic antimyeloid activity in combination with CXCR4 antagonists. Blood. 2010;116:5306–5315.
  • Spinello I, Quaranta MT, Riccioni R, et al. MicroRNA-146a and AMD3100, two ways to control CXCR4 expression in acute myeloid leukemias. Blood Cancer J. 2011;1:e26.
  • Li X, Xu S, Tan Y, et al. The effects of idarubicin versus other anthracyclines for induction therapy of patients with newly diagnosed leukaemia. Cochrane Database Syst Rev. 2015;6:CD010432.
  • Maiso P, Colado E, Ocio EM, et al. The synergy of panobinostat plus doxorubicin in acute myeloid leukemia suggests a role for HDAC inhibitors in the control of DNA repair. Leukemia. 2009;23:2265–2274.
  • Tazzari PL, Cappellini A, Ricci F, et al. Multidrug resistance-associated protein 1 expression is under the control of the phosphoinositide 3 kinase/Akt signal transduction network in human acute myelogenous leukemia blasts. Leukemia. 2007;21:427–438.
  • Jiang XJ, Huang KK, Yang M, et al. Synergistic effect of panobinostat and bortezomib on chemoresistant acute myelogenous leukemia cells via AKT and NF-κB pathways. Cancer Lett. 2012;326:135–142.
  • Corrales-Medina FF, Manton CA, Orlowski RZ, et al. Efficacy of panobinostat and marizomib in acute myeloid leukemia and bortezomib-resistant models. Leuk Res. 2015;39:371–379.
  • Cilloni D, Renneville A, Hermitte F, et al. Real-time quantitative polymerase chain reaction detection of minimal residual disease by standardized WT1 assay to enhance risk stratification in acute myeloid leukemia: a European Leukemia Net study. J Clin Oncol. 2009;27:5195–5201.
  • Yan-Fang T, Zhi-Heng L, Li-Xiao X, et al. Molecular mechanism of the cell death induced by the histone deacetylase pan inhibitor LBH589 (Panobinostat) in Wilms tumor cells. PLoS One. 2015;10:e0126566.
  • Giles F, Fischer T, Cortes J, et al. A phase I study of intravenous LBH589, a novel cinnamic hydroxamic acid analogue histone deacetylase inhibitor, in patients with refractory hematologic malignancies. Clin Cancer Res. 2006;12:4628–4635.
  • De Angelo DJ, Spencer A, Bhalla KN, et al. Phase Ia/II, two-arm, open-label, dose-escalation study of oral panobinostat administered via two dosing schedules in patients with advanced hematologic malignancies. Leukemia. 2013;27:1628–1636.
  • Byrd JC, Marcucci G, Parthun MR, et al. A phase 1 and pharmacodynamic study of depsipeptide (fk228) in chronic lymphocytic leukemia and acute myeloid leukemia. Blood. 2005;105:959–967.
  • Klimek VM, Fircanis S, Maslak P, et al. Tolerability, pharmacodynamics, and pharmacokinetics studies of depsipeptide (romidepsin) in patients with acute myelogenous leukemia or advanced myelodysplastic syndromes. Clinical Can Res. 2008;14:826–832.
  • Gojo I, Jiemjit A, Trepel JB, et al. Phase 1 and pharmacologic study of ms-275, a histone deacetylase inhibitor, in adults with refractory and relapsed acute leukemias. Blood. 2007;109:2781–2790.
  • Quintás-Cardama A, Santos FP, Garcia-Manero G. Histone deacetylase inhibitors for the treatment of myelodysplastic syndrome and acute myeloid leukemia. Leukemia. 2011;2:226–235.
  • 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: PETHEMA Group. Haematologica. 2015;100:1294–1300.
  • Long J, Chang L, Shen Y, et al. Valproic acid ameliorates graft-versus-host disease by downregulating Th1 and Th17 cells. J Immunol. 2015;195:1849–1857.
  • Ersvaer E, Liseth K, Skavland J, et al. Intensive chemotherapy for acute myeloid leukemia differentially affects circulating TC1, Th1, Th17 and TREG cells. BMC Immunol. 2010;11:38–10.
  • Williams KM, Hakim FT, Gress RE. T cell immune reconstitution following lymphodepletion. Semin Immunol. 2007;19:318–330.
  • Shenghui Z, Yixiang H, Jianbo W, et al. Elevated frequencies of CD4 CD25 CD127lo regulatory T cells is associated to poor prognosis in patients with acute myeloid leukemia. Int J Cancer. 2011;129:1373–138.
  • Szczepanski MJ, Szajnik M, Czystowska M, et al. Increased frequency and suppression by regulatory T cells in patients with acute myelogenous leukemia. Clin Cancer Res. 2009;15:3325–3332.
  • Wu C, Wang S, Wang F, et al. Increased frequencies of T helper type 17 cells in the peripheral blood of patients with acute myeloid leukemia. Clin Exp Immunol. 2009;158:199–204.
  • Fredly H, Ersvær 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;5:13.
  • Shen L, Pili R. Class I histone deacetylase inhibition is a novel mechanism to target regulatory T cells in immunotherapy. Oncoimmunology. 2012;1:948–950.
  • Yang W, Xu Y. Clinical significance of Treg cell frequency in acute myeloid leukemia. Int J Hematol. 2013;98:558–562.
  • Govindaraj C, Tan P, Walker P, et al. Reducing TNF receptor 2+ regulatory T cells via the combined action of azacitidine and the HDAC inhibitor, panobinostat for clinical benefit in acute myeloid leukemia patients. Clin Cancer Res. 2014;20:724–735.
  • Bug G, Burchert A, Nicolaus K, et al. Post-transplant maintenance with the deacetylase inhibitor panobinostat in patients with high-risk AML or MDS: results of the phase I part of the Panobest trial [abstract no. 3315]. In: 55th Annual Meeting and Exposition of the American Society of Hematology. ASH Blood. 2013;122:3315.
  • Kuendgen A, Knipp S, Fox F, et al. Results of a phase 2 study of valproic acid alone or in combination with all-trans retinoic acid in 75 patients with myelodysplastic syndrome and relapsed or refractory acute myeloid leukemia. Ann Hematol. 2005;84(Suppl 1):61–66.
  • Kuendgen A, Schmid M, Schlenk R, et al. The histone deacetylase (HDAC) inhibitor valproic acid as monotherapy or in combination with all-trans retinoic acid in patients with acute myeloid leukemia. Cancer. 2006;106:112–119.
  • Rasheed W, Bishton M, Johnstone RW, et al. Histone deacetylase inhibitors in lymphoma and solid malignancies. Expert Rev Anticancer Ther. 2008;8:413–432.
  • Khot A, Dickinson M, Prince HM. Panobinostat in lymphoid and myeloid malignancies. Expert Opin Investig Drugs. 2013;22:1211–1223.
  • Niesvizky R, Ely S, Mark T, et al. Phase 2 trial of the histone deacetylase inhibitor romidepsin for the treatment of refractory MM. Cancer. 2011;117:336–342.
  • Aaronson NK, Ahmedzai S, Bergman B, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993;85:365–376.
  • Deschler B, Ihorst G, Platzbecker U, et al. Parameters detected by geriatric and quality of life assessment in 195 older patients with myelodysplastic syndromes and acute myeloid leukemia are highly predictive for outcome. Haematologica. 2013;98:208–216.
  • Timmermann S, Lehrmann H, Polesskaya A, et al. Histone acetylation and disease. Cell Mol Life Sci. 2001;58(5–6):728–736.
  • Schaefer EW, Loaiza-Bonilla A, Juckett M, et al. A phase 2 study of vorinostat in acute myeloid leukemia. Haematologica. 2009;94:1375–1382.
  • Walter RB, Medeiros BC, Powell BL, et al. Phase II trial of vorinostat and gemtuzumab ozogamicin as induction and post-remission therapy in older adults with previously untreated acute myeloid leukemia. Haematologica. 2012;97:739–742.
  • Montalban-Bravo G, Garcia-Manero G. Novel drugs for older patients with acute myeloid leukemia. Leukemia. 2015;29:760–769.
  • Göttlicher M, Minucci S, Zhu P, et al. Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells. EMBO J. 2001;20:6969–6978.
  • Tassara M, Döhner K, Brossart P, et al. Valproic acid in combination with all-trans retinoic acid and intensive therapy for acute myeloid leukemia in older patients. Blood. 2014;123:4027–4036.
  • Silverman LV, Odchimar-Reissig A, Cozza R, et al. A phase I/II study of vorinostat, an oral histone deacetylase inhibitor, in combination with azacitidine in patients with myelodysplastic syndrome and acute myeloid leukemia (AML). Initial results of the phase I trial: a New York Cancer Consortium. J Clin Oncol. 2008;26(suppl):Abstract7000.
  • Cancer Genome Atlas Research Network. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med. 2013 May 30;368:2059–2074.
  • Khwaja A, Bjorkholm M, Gale RE, et al. Acute myeloid leukaemia. Nat Rev Dis Primers. 2016;2:16010.
  • Malcovati L, Papaemmanuil E, Ambaglio I, et al. Driver somatic mutations identify distinct disease entities within myeloid neoplasms with myelodysplasia. Blood. 2014;124:1513–1521.
  • Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–674.
  • Vogelstein B, Papadopoulos N, Velculescu VE, et al. Cancer genome landscapes. Science. 2013;339:1546–1558.
  • Kandoth C, McLellan MD, Vandin F, et al. Mutational landscape and significance across 12 major cancer types. Nature. 2013;502:333–339.
  • Levitzki A. Tyrosine kinase inhibitors: views of selectivity, sensitivity, and clinical performance. Annu Rev Pharmacol Toxicol. 2013;53:161–185.
  • Garraway LA, Baselga J. Whole-genome sequencing and cancer therapy: is too much ever enough? Cancer Discov. 2012;2:766–768.
  • Hartwell LH, Szankasi P, Roberts CJ, et al. Integrating genetic approaches into the discovery of anticancer drugs. Science. 1997;278:1064–1068.
  • Fece de la Cruz F, Gapp BV, Nijman SM. Synthetic lethal vulnerabilities of cancer. Annu Rev Pharmacol Toxicol. 2015;55:513–531.
  • Ogiwara H, Sasaki M, Mitachi T, et al. Targeting p300 addiction in CBP-deficient cancers causes synthetic lethality by apoptotic cell death due to abrogation of MYC expression. Cancer Discov. 2016;6:430–445.
  • Aerts S, Cools J. Cancer: mutations close in on gene regulation. Nature. 2013;499:35–36.
  • Patel JP, Gönen M, Figueroa ME, et al. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med. 2012;366:1079–1089.

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