Emerging therapeutic targets in human acute myeloid leukemia (part 2) – bromodomain inhibition should be considered as a possible strategy for various patient subsets

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 LeukemiaNet. Blood 2010;115(3):453-74
   PubMed Web of Science ®Google Scholar
• Stapnes C, Gjertsen BT, Reikvam H, Bruserud O. Targeted therapy in acute myeloid leukaemia: current status and future directions. Expert Opin Investig Drugs 2009;18(4):433-55
   PubMed Web of Science ®Google Scholar
• Reikvam H, Hatfield KJ, Fredly H, et al. The angioregulatory cytokine network in human acute myeloid leukemia - from leukemogenesis via remission induction to stem cell transplantation. Eur Cytokine Netw 2012;23(4):140-53
   PubMed Web of Science ®Google Scholar
• Reikvam H, Hatfield KJ, Lassalle P, et al. Targeting the angiopoietin (Ang)/Tie-2 pathway in the crosstalk between acute myeloid leukaemia and endothelial cells: studies of Tie-2 blocking antibodies, exogenous Ang-2 and inhibition of constitutive agonistic Ang-1 release. Expert Opin Investig Drugs 2010;19(2):169-83
   PubMed Web of Science ®Google Scholar
• Hatfield KJ, Olsnes AM, Gjertsen BT, Bruserud O. Antiangiogenic therapy in acute myelogenous leukemia: targeting of vascular endothelial growth factor and interleukin 8 as possible antileukemic strategies. Curr Cancer Drug Targets 2005;5(4):229-48
   PubMed Web of Science ®Google Scholar
• Wellbrock J, Fiedler W. Clinical experience with antiangiogenic therapy in leukemia. Curr Cancer Drug Targets 2011;11(9):1053-68
   PubMedGoogle Scholar
• Tsykunova G, Reikvam H, Ahmed AB, et al. Targeting of polo-like kinases and their cross talk with Aurora kinases--possible therapeutic strategies in human acute myeloid leukemia? Expert Opin Investig Drugs 2012;21(5):587-603
   PubMed Web of Science ®Google Scholar
• 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):761-76
   PubMed Web of Science ®Google Scholar
• 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(4):468-80
   PubMed Web of Science ®Google Scholar
• 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(5):551-63
   PubMed Web of Science ®Google Scholar
• 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(8):929-44
   PubMed Web of Science ®Google Scholar
• Reikvam H, Olsnes AM, Gjertsen BT, et al. Nuclear factor-kappaB signaling: a contributor in leukemogenesis and a target for pharmacological intervention in human acute myelogenous leukemia. Crit Rev Oncog 2009;15(1-2):1-41
   PubMedGoogle Scholar
• Bruserud O, Reikvam H. Therapeutic targeting of NF-kappaB in myelodysplastic syndromes and acute myeloid leukaemia - the biological heterogeneity. Expert Opin Ther Targets 2010;14(11):1139-42
   PubMed Web of Science ®Google Scholar
• Reikvam H, Tamburini J, Skrede S, et al. Antileukaemic effect of PI3K-mTOR inhibitors in acute myeloid leukaemia-gene expression profiles reveal CDC25B expression as determinate of pharmacological effect. Br J Haematol 2014;164(2):200-11
   PubMed Web of Science ®Google Scholar
• Reikvam H, Nepstad I, Tamburini J. Predicting effects of kinase inhibitor in therapy for myeloid malignancies - the challenges in capturing disease heterogeneity. Expert Opin Investig Drugs 2013;22(11):1365-70
   PubMed Web of Science ®Google Scholar
• Martelli AM, Evangelisti C, Chiarini F, et al. Targeting the PI3K/AKT/mTOR signaling network in acute myelogenous leukemia. Expert Opin Investig Drugs 2009;18(9):1333-49
   PubMed Web of Science ®Google Scholar
• Weisberg E, Barrett R, Liu Q, et al. FLT3 inhibition and mechanisms of drug resistance in mutant FLT3-positive AML. Drug Res Updates 2009;12(3):81-9
   Google Scholar
• Bruserud O, Nepstad I, Hauge M, et al. STAT3 as a possible therapeutic target in human malignancies: Lessions from acute myeloid leukemia. Exp Rev Hematol 2014;6:1-13
   Google Scholar
• Berger SL, Kouzarides T, Shiekhattar R, Shilatifard A. An operational definition of epigenetics. Genes Dev 2009;23(7):781-3
   PubMed Web of Science ®Google Scholar
• Morin A, Letouze E, Gimenez-Roqueplo AP, Favier J. Oncometabolites-driven tumorigenesis: From genetics to targeted therapy. Int J Cancer 2014;135(10):2237-48
   Google Scholar
• Greenblatt SM, Nimer SD. Chromatin modifiers and the promise of epigenetic therapy in acute leukemia. Leukemia 2014;28(7):1396-406
   PubMed Web of Science ®Google Scholar
• Abdel-Wahab O, Levine RL. Mutations in epigenetic modifiers in the pathogenesis and therapy of acute myeloid leukemia. Blood 2013;121(18):3563-72
   PubMed Web of Science ®Google Scholar
• Neff T, Armstrong SA. Recent progress toward epigenetic therapies: the example of mixed lineage leukemia. Blood 2013;121(24):4847-53
   PubMedGoogle Scholar
• Mayer J, Arthur C, Delaunay J, et al. Multivariate and subgroup analyses of a randomized, multinational, phase 3 trial of decitabine vs treatment choice of supportive care or cytarabine in older patients with newly diagnosed acute myeloid leukemia and poor- or intermediate-risk cytogenetics. BMC Cancer 2014;14:69
   PubMed Web of Science ®Google Scholar
• Garcia-Manero G, Jabbour E, Borthakur G, et al. Randomized open-label phase II study of decitabine in patients with low- or intermediate-risk myelodysplastic syndromes. J Clin Oncol 2013;31(20):2548-53
   PubMed Web of Science ®Google Scholar
• Fenaux P, Mufti GJ, Hellstrom-Lindberg E, et al. Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia. J Clin Oncol 2010;28(4):562-9
   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 Epigenet 2013;5(1):12
   PubMed Web of Science ®Google Scholar
• Bruserud O, Stapnes C, Ersvaer E, et al. Histone deacetylase inhibitors in cancer treatment: a review of the clinical toxicity and the modulation of gene expression in cancer cell. Curr Pharm Biotechnol 2007;8(6):388-400
   PubMed Web of Science ®Google Scholar
• Conway O’Brien E, Prideaux S, Chevassut T. The epigenetic landscape of acute myeloid leukemia. Adv Hematol 2014;2014:103175
   PubMedGoogle Scholar
• Kouzarides T. Chromatin modifications and their function. Cell 2007;128(4):693-705
   PubMed Web of Science ®Google Scholar
• Dhalluin C, Carlson JE, Zeng L, et al. Structure and ligand of a histone acetyltransferase bromodomain. Nature 1999;399(6735):491-6
   PubMed Web of Science ®Google Scholar
• Mujtaba S, He Y, Zeng L, et al. Structural basis of lysine-acetylated HIV-1 Tat recognition by PCAF bromodomain. Mol Cell 2002;9(3):575-86
   PubMed Web of Science ®Google Scholar
• Mujtaba S, He Y, Zeng L, et al. Structural mechanism of the bromodomain of the coactivator CBP in p53 transcriptional activation. Mol Cell 2004;13(2):251-63
   PubMed Web of Science ®Google Scholar
• Wu SY, Chiang CM. The double bromodomain-containing chromatin adaptor Brd4 and transcriptional regulation. J Biol Chem 2007;282(18):13141-5
   PubMed Web of Science ®Google Scholar
• Weidner-Glunde M, Ottinger M, Schulz TF. WHAT do viruses BET on? Front Biosci 2010;15:537-49
   Google Scholar
• Kellner WA, Van Bortle K, Li L, et al. Distinct isoforms of the Drosophila Brd4 homologue are present at enhancers, promoters and insulator sites. Nucleic Acids Res 2013;41(20):9274-83
   Google Scholar
• Dey A, Ellenberg J, Farina A, et al. A bromodomain protein, MCAP, associates with mitotic chromosomes and affects G(2)-to-M transition. Mol Cell Biol 2000;20(17):6537-49
   PubMed Web of Science ®Google Scholar
• Pericole FV, Roversi FM, Duarte ASS, et al. BRD4 short isoform is a myelodysplasia prognostic marker involved in inappropriate DNA damage response. Abstract no 3234 ASH Annual Meeting Abstracts; 2014
   Google Scholar
• Devaiah BN, Lewis BA, Cherman N, et al. BRD4 is an atypical kinase that phosphorylates serine2 of the RNA polymerase II carboxy-terminal domain. Proc Natl Acad Sci USA 2012;109(18):6927-32
   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):524-8
   PubMed Web of Science ®Google Scholar
• Stewart HJ, Horne GA, Bastow S, Chevassut TJ. BRD4 associates with p53 in DNMT3A-mutated leukemia cells and is implicated in apoptosis by the bromodomain inhibitor JQ1. Cancer Med 2013;2(6):826-35
   PubMed Web of Science ®Google Scholar
• Goupille O, Penglong T, Lefevre C, et al. BET bromodomain inhibition rescues erythropoietin differentiation of human erythroleukemia cell line UT7. Biochem Biophys Res Commun 2012;429(1-2):1-5
   PubMed Web of Science ®Google Scholar
• Hewings DS, Fedorov O, Filippakopoulos P, et al. Optimization of 3,5-dimethylisoxazole derivatives as potent bromodomain ligands. J Med Chem 2013;56(8):3217-27
   PubMed Web of Science ®Google Scholar
• Devaraj SGT, Fiskus W, Shah B, et al. Mechanistic role of HEXIM1 induction in BRD4-antagonist mediated growth inhibition, differentiation and in vivo lethal activity against human aml blast progenitor cells. Abstract no 3534 ASH (American Society for Hematology) Annual Meeting Abstracts; 2014
   Google Scholar
• Coudé M-M, Braun T, Berrou J, et al. Bromodomain inhibition by OTX015 Regulates c-MYC and HEXIM1 in a panel of human acute leukemia cell lines. Abstract no 5957 ASH Annual Meeting Abstracts; 2014
   Google Scholar
• Carlson S, Glass KC. The MOZ histone acetyltransferase in epigenetic signaling and disease. J Cell Physiol 2014;229(11):1571-4
   Google Scholar
• Reikvam H, Hatfield KJ, Kittang AO, et al. Acute Myeloid Leukemia with the t(8;21) Translocation: Clinical Consequences and Biological Implications. J Biomed Biotechnol 2011;2011:104631
   PubMedGoogle Scholar
• Shima H, Yamagata K, Aikawa Y, et al. Bromodomain-PHD finger protein 1 is critical for leukemogenesis associated with MOZ-TIF2 fusion. Int J Hematol 2014;99(1):21-31
   PubMed Web of Science ®Google Scholar
• Aikawa Y, Katsumoto T, Zhang P, et al. PU.1-mediated upregulation of CSF1R is crucial for leukemia stem cell potential induced by MOZ-TIF2. Nat Med 2010;16(5):580-5. 581p following 585
   Google Scholar
• Rokudai S, Aikawa Y, Tagata Y, et al. Monocytic leukemia zinc finger (MOZ) interacts with p53 to induce p21 expression and cell-cycle arrest. J Biol Chem 2009;284(1):237-44
   PubMed Web of Science ®Google Scholar
• Rowley JD. The critical role of chromosome translocations in human leukemias. Annu Rev Genet 1998;32:495-519
   PubMed Web of Science ®Google Scholar
• Thirman MJ, Gill HJ, Burnett RC, et al. Rearrangement of the MLL gene in acute lymphoblastic and acute myeloid leukemias with 11q23 chromosomal translocations. N Engl J Med 1993;329(13):909-14
   PubMed Web of Science ®Google Scholar
• Popovic R, Zeleznik-Le NJ. MLL: how complex does it get? J Cell Biochem 2005;95(2):234-42
   PubMed Web of Science ®Google Scholar
• Lavau C, Du C, Thirman M, Zeleznik-Le N. Chromatin-related properties of CBP fused to MLL generate a myelodysplastic-like syndrome that evolves into myeloid leukemia. EMBO J 2000;19(17):4655-64
   PubMed Web of Science ®Google Scholar
• Wu T, Zhang X, Huang X, et al. Regulation of cyclin B2 expression and cell cycle G2/m transition by menin. J Biol Chem 2010;285(24):18291-300
   Google Scholar
• Zhang Y, Chen A, Yan XM, Huang G. Disordered epigenetic regulation in MLL-related leukemia. Int J Hematol 2012;96(4):428-37
   PubMed Web of Science ®Google Scholar
• Thiel AT, Huang J, Lei M, Hua X. Menin as a hub controlling mixed lineage leukemia. Bioessays 2012;34(9):771-80
   PubMed Web of Science ®Google Scholar
• Dawson MA, Prinjha RK, Dittmann A, et al. Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. Nature 2011;478(7370):529-33
   PubMed Web of Science ®Google Scholar
• Dawson MA, Gudgin EJ, Horton SJ, et al. Recurrent mutations, including NPM1c, activate a BRD4-dependent core transcriptional program in acute myeloid leukemia. Leukemia 2014;28(2):311-20
   PubMed Web of Science ®Google Scholar
• Mannervik M, Nibu Y, Zhang H, Levine M. Transcriptional coregulators in development. Science 1999;284(5414):606-9
   Google Scholar
• Bannister AJ, Kouzarides T. The CBP co-activator is a histone acetyltransferase. Nature 1996;384(6610):641-3
   PubMed Web of Science ®Google Scholar
• Santillan DA, Theisler CM, Ryan AS, et al. Bromodomain and histone acetyltransferase domain specificities control mixed lineage leukemia phenotype. Cancer Res 2006;66(20):10032-9
   PubMed Web of Science ®Google Scholar
• Luo Z, Lin C, Shilatifard A. The super elongation complex (SEC) family in transcriptional control. Nat Rev Mol Cell Biol 2012;13(9):543-7
   PubMed Web of Science ®Google Scholar
• Smith E, Lin C, Shilatifard A. The super elongation complex (SEC) and MLL in development and disease. Genes Dev 2011;25(7):661-72
   PubMed Web of Science ®Google Scholar
• Patel JP, Gonen M, Figueroa ME, et al. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med 2012;366(12):1079-89
   PubMed Web of Science ®Google Scholar
• Reikvam H, Bruserud Ø. Emerging therapeutic targets for the treatment of human acute myeloid leukemia (PART 1) - gene transcription, cell cycle regulation, metabolism and intercellular communication. Exp Rev Hematol Submitted 2015 [Epub ahead of print]
   Google Scholar
• Riveiro ME, Astorgues-Xerri L, Canet-jourdan C, et al. Preclinical Evaluation of the BET-Bromodomain (BET-BRD) Inhibitor OTX015 in Leukemia Cell Lines Harboring the JAK2 V617F Mutation. Abstract no 873 ASH Annual Meeting Abstracts 2014
   Google Scholar
• Rodriguez M, Fiskus W, Sharma S, et al. Abstract 1721: BRD4 antagonist-based therapy exerts lethal activity against FLT3 mutation expressing AML cells resistant to FLT3 tyrosine kinase inhibitors. Cancer Res 2014;74(19 Suppl):1721
   Google Scholar
• Chen C, Liu Y, Lu C, et al. Cancer-associated IDH2 mutants drive an acute myeloid leukemia that is susceptible to Brd4 inhibition. Genes Dev 2013;27(18):1974-85
   PubMed Web of Science ®Google Scholar
• Muntean AG, Hess JL. The pathogenesis of mixed-lineage leukemia. Ann Rev Pathol 2012;7:283-301
   PubMed Web of Science ®Google Scholar
• Ayton PM, Chen EH, Cleary ML. Binding to nonmethylated CpG DNA is essential for target recognition, transactivation, and myeloid transformation by an MLL oncoprotein. Mol Cell Biol 2004;24(23):10470-8
   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 USA 2011;108(38):15751-6
   PubMed Web of Science ®Google Scholar
• Chang MJ, Wu H, Achille NJ, et al. Histone H3 lysine 79 methyltransferase Dot1 is required for immortalization by MLL oncogenes. Cancer Res 2010;70(24):10234-42
   PubMed Web of Science ®Google Scholar
• Chen L, Deshpande AJ, Banka D, et al. Abrogation of MLL-AF10 and CALM-AF10-mediated transformation through genetic inactivation or pharmacological inhibition of the H3K79 methyltransferase Dot1l. Leukemia 2013;27(4):813-22
   PubMed Web of Science ®Google Scholar
• Daigle SR, Olhava EJ, Therkelsen CA, et al. Selective killing of mixed lineage leukemia cells by a potent small-molecule DOT1L inhibitor. Cancer Cell 2011;20(1):53-65
   PubMed Web of Science ®Google Scholar
• Daigle SR, Olhava EJ, Therkelsen CA, et al. Potent inhibition of DOT1L as treatment of MLL-fusion leukemia. Blood 2013;122(6):1017-25
   PubMed Web of Science ®Google Scholar
• Basavapathruni A, Olhava EJ, Daigle SR, et al. Nonclinical pharmacokinetics and metabolism of EPZ-5676, a novel DOT1L histone methyltransferase inhibitor. Biopharm Drug Disp 2014;35(4):237-52
   PubMed Web of Science ®Google Scholar
• Dose escalation study of EPZ-5676 in pediatric patients with leukemias bearing a rearrangement of the MLL Gene. Available from: https://clinicaltrials.gov/ct2/show/NCT02141828
   Google Scholar
• A first-in-human Phase 1 and expanded cohort study of EPZ-5676 in advanced hematologic malignancies, including acute leukemia with rearrangement of the MLL Gene. Available from: https://clinicaltrials.gov/ct2/show/NCT01684150
   Google Scholar
• McLean CM, Karemaker ID, van Leeuwen F. The emerging roles of DOT1L in leukemia and normal development. Leukemia 2014;28(11):2131-8
   PubMed Web of Science ®Google Scholar
• Kuhn MW, Hadler MJ, Daigle SR, et al. MLL partial tandem duplication leukemia cells are sensitive to small molecule DOT1L inhibition. Haematologica 2015. [Epub ahead of print]
   Google Scholar
• Rau RE, Luo M, Rodriguez B, et al. DOT1L as a therapeutic target for the treatment of DNMT3A-mutant acute myeloid leukemia. Abstract no 614 ASH Annual Meeting Abstracts; 2014
   Google Scholar
• Carew JS, Espitia CM, Zhao W, et al. Targeting HDAC6 Is a novel approach to augment the therapeutic benefit of bromodomain inhibition in multiple myeloma. Abstract no 4760 ASH Annual Meeting Abstracts; 2014
   Google Scholar
• Knutson SK, Wigle TJ, Warholic NM, et al. A selective inhibitor of EZH2 blocks H3K27 methylation and kills mutant lymphoma cells. Nat Chem Biol 2012;8(11):890-6
   PubMed Web of Science ®Google Scholar
• Knutson SK, Kawano S, Minoshima Y, et al. Selective inhibition of EZH2 by EPZ-6438 leads to potent antitumor activity in EZH2-mutant non-Hodgkin lymphoma. Mol Cancer Ther 2014;13(4):842-54
   PubMed Web of Science ®Google Scholar
• Sinha S, Thomas D, Yu L, et al. Mutant WT1 is associated with DNA hypermethylation of PRC2 targets in AML and responds to EZH2 inhibition. Blood 2015;125(2):316-26
   Google Scholar
• Xu B, On DM, Ma A, et al. Selective inhibition of EZH2 and EZH1 enzymatic activity by a small molecule suppresses MLL-rearranged leukemia. Blood 2015;125(2):346-57
   PubMed Web of Science ®Google Scholar
• Walsby E, Lazenby M, Pepper C, Burnett AK. The cyclin-dependent kinase inhibitor SNS-032 has single agent activity in AML cells and is highly synergistic with cytarabine. Leukemia 2011;25(3):411-19
   PubMed Web of Science ®Google Scholar
• Grosjean-Raillard J, Tailler M, Ades L, et al. ATM mediates constitutive NF-kappaB activation in high-risk myelodysplastic syndrome and acute myeloid leukemia. Oncogene 2009;28(8):1099-109
   Google Scholar
• Yamauchi T, Uzui K, Nishi R, et al. Gemtuzumab ozogamicin and olaparib exert synergistic cytotoxicity in CD33-positive HL-60 myeloid leukemia cells. Anticancer Res 2014;34(10):5487-94
   Google Scholar
• Kaufman B, Shapira-Frommer R, Schmutzler RK, et al. Olaparib Monotherapy in Patients With Advanced Cancer and a Germline BRCA1/2 Mutation. J Clin Oncol 2015;33(3):244-50
   PubMed Web of Science ®Google Scholar
• Walter RB. Biting back: BiTE antibodies as a promising therapy for acute myeloid leukemia. Expert Rev Hematol 2014;7(3):317-19
   PubMed Web of Science ®Google Scholar
• Marin-Hernandez A, Gallardo-Perez JC, Ralph SJ, et al. HIF-1alpha modulates energy metabolism in cancer cells by inducing over-expression of specific glycolytic isoforms. Mini Rev Med Chem 2009;9(9):1084-101
   PubMed Web of Science ®Google Scholar
• Amann T, Hellerbrand C. GLUT1 as a therapeutic target in hepatocellular carcinoma. Expert Opin Ther Targets 2009;13(12):1411-27
   PubMed Web of Science ®Google Scholar
• Barnes K, Ingram JC, Porras OH, et al. Activation of GLUT1 by metabolic and osmotic stress: potential involvement of AMP-activated protein kinase (AMPK). J Cell Sci 2002;115(Pt 11):2433-42
   Google Scholar
• Helleday T. Cancer phenotypic lethality, exemplified by the non-essential MTH1 enzyme being required for cancer survival. Ann Oncol 2014;25(7):1253-5
   Google Scholar
• Huber KV, Salah E, Radic B, et al. Stereospecific targeting of MTH1 by (S)-crizotinib as an anticancer strategy. Nature 2014;508(7495):222-7
   PubMed Web of Science ®Google Scholar
• Gad H, Koolmeister T, Jemth AS, et al. MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool. Nature 2014;508(7495):215-21
   PubMed Web of Science ®Google Scholar
• Hatfield KJ, Reikvam H, Bruserud O. Identification of a subset of patients with acute myeloid leukemia characterized by long-term in vitro proliferation and altered cell cycle regulation of the leukemic cells. Expert Opin Ther Targets 2014;18(11):1237-51
   PubMed Web of Science ®Google Scholar
• Bruserud O, Gjertsen BT, Foss B, Huang TS. New strategies in the treatment of acute myelogenous leukemia (AML): in vitro culture of aml cells--the present use in experimental studies and the possible importance for future therapeutic approaches. Stem Cells 2001;19(1):1-11
   PubMed Web of Science ®Google Scholar
• Eppert K, Takenaka K, Lechman ER, et al. Stem cell gene expression programs influence clinical outcome in human leukemia. Nat Med 2011;17(9):1086-93
   PubMed Web of Science ®Google Scholar
• Shlush LI, Zandi S, Mitchell A, et al. Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia. Nature 2014;506(7488):328-33
   PubMed Web of Science ®Google Scholar
• Hartmann L, Stephenson CF, Verkamp SR, et al. Detection of clonal evolution in hematopoietic malignancies by combining comparative genomic hybridization and single nucleotide polymorphism arrays. Clin Chem 2014;60(12):1558-68
   Google Scholar
• Network CGAR. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med 2013;368(22):2059-74
   PubMed Web of Science ®Google Scholar
• Bolden JE, Tasdemir N, Dow LE, et al. Inducible in vivo silencing of Brd4 identifies potential toxicities of sustained BET protein inhibition. Cell Rep 2014;8(6):1919-29
   PubMed Web of Science ®Google Scholar
• Stein EM, Garcia-Manero G, Rizzieri DA, et al. The DOT1L Inhibitor EPZ-5676: safety and activity in relapsed/refractory patients with MLL-rearranged leukemia. Abstract no 387 ASH Annual Meeting Abstracts; 2014
   Google Scholar
• Maus MV, June CH. CARTs on the road for myeloma. Clin Cancer Res 2014;20(15):3899-901
   PubMed Web of Science ®Google Scholar
• Pizzitola I, Anjos-Afonso F, Rouault-Pierre K, et al. Chimeric antigen receptors against CD33/CD123 antigens efficiently target primary acute myeloid leukemia cells in vivo. Leukemia 2014;28(8):1596-605
   PubMed Web of Science ®Google Scholar
• Gill S, Tasian SK, Ruella M, et al. Preclinical targeting of human acute myeloid leukemia and myeloablation using chimeric antigen receptor-modified T cells. Blood 2014;123(15):2343-54
   PubMed Web of Science ®Google Scholar
• Sasine JP, Schiller GJ. Emerging strategies for high-risk and relapsed/refractory acute myeloid leukemia: Novel agents and approaches currently in clinical trials. Blood Rev 2015;29(1):1-9
   PubMed Web of Science ®Google Scholar
• O’Hear C, Heiber JF, Schubert I, et al. Anti-CD33 chimeric antigen receptor targeting of acute myeloid leukemia. Haematologica 2015;100(3):336-44
   PubMed Web of Science ®Google Scholar