A Druggable TCF4- and BRD4-Dependent Transcriptional Network Sustains Malignancy in Blastic Plasmacytoid Dendritic Cell Neoplasm

Cancer Cell

Volumn 30, Issue 5, 2016, Pages 764-778

  Ceribelli, Michele ^a,e   Hou, Zhiying Esther ^b   Kelly, Priscilla N ^a   Huang, Da Wei ^a   Wright, George ^a   Ganapathi, Karthik ^a,b   Evbuomwan, Moses O ^a   Pittaluga, Stefania ^a   Shaffer, Arthur L ^a   Marcucci, Guido ^c   Forman, Stephen J ^c   Xiao, Wenming ^d   Guha, Rajarshi ^e   Zhang, Xiaohu ^e   Ferrer, Marc ^e   Chaperot, Laurence ^f,g   Plumas, Joel ^f,g   Jaffe, Elaine S ^a   Thomas, Craig J ^e   Reizis, Boris ^b,h   Staudt, Louis M ^a   more..

^a NATIONAL CANCER INSTITUTE   (United States)

^b New York Presbyterian Morgan Stanley Children's Hospital   (United States)

^c CITY OF HOPE NATIONAL MEDICAL CENTER   (United States)

^d NATIONAL CENTER FOR TOXICOLOGICAL RESEARCH   (United States)

^e NATIONAL INSTITUTES OF HEALTH   (United States)

^f ETABLISSEMENT FRANÇAIS DU SANG   (France)

^g INSTITUTE FOR ADVANCED BIOSCIENCES   (France)

^h NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

BPDCN; BRD4; HTS; super enhancer; TCF4

Indexed keywords

4 (4 CHLOROPHENYL) 2,3,9 TRIMETHYL 6H THIENO[3,2 F][1,2,4]TRIAZOLO[4,3 A][1,4]DIAZEPINE 6 ACETIC ACID TERT BUTYL ESTER; BROMODOMAIN INHIBITOR; CASPASE 3; CD8ALPHA ANTIGEN; INTERFERON CONSENSUS SEQUENCE BINDING PROTEIN; INTERLEUKIN 3 RECEPTOR; MESSENGER RNA; MYC PROTEIN; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE 1; PROTEIN BCL 2; SHORT HAIRPIN RNA; TOLL LIKE RECEPTOR 9; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR TCF4; UNCLASSIFIED DRUG; BASIC HELIX LOOP HELIX LEUCINE ZIPPER TRANSCRIPTION FACTOR; BRD4 PROTEIN, HUMAN; MOLECULAR LIBRARY; NUCLEAR PROTEIN; SMALL INTERFERING RNA; TCF4 PROTEIN, HUMAN;

ACUTE MYELOID LEUKEMIA; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BLASTIC PLASMACYTOID DENDRITIC CELL NEOPLASM; CELL CYCLE G2 PHASE; CELL CYCLE S PHASE; CELL PROLIFERATION; GENE EXPRESSION; GRANULOCYTIC SARCOMA; HEMATOLOGIC MALIGNANCY; HIGH THROUGHPUT SCREENING; HUMAN; MOLECULARLY TARGETED THERAPY; NONHUMAN; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; PROTEIN CLEAVAGE; RNA INTERFERENCE; TUMOR XENOGRAFT; ADMINISTRATION AND DOSAGE; ANIMAL; ANTAGONISTS AND INHIBITORS; DENDRITIC CELL; DRUG SCREENING; GENE EXPRESSION REGULATION; GENE REGULATORY NETWORK; GENETICS; HEMATOLOGIC NEOPLASMS; HL-60 CELL LINE; JURKAT CELL LINE; METABOLISM; MOLECULAR LIBRARY; MOUSE; PATHOLOGY; PHARMACOLOGY; TUMOR CELL LINE;

ANIMALS; BASIC HELIX-LOOP-HELIX LEUCINE ZIPPER TRANSCRIPTION FACTORS; CELL LINE, TUMOR; DENDRITIC CELLS; GENE EXPRESSION REGULATION, NEOPLASTIC; GENE REGULATORY NETWORKS; HEMATOLOGIC NEOPLASMS; HL-60 CELLS; HUMANS; JURKAT CELLS; MICE; NUCLEAR PROTEINS; RNA, SMALL INTERFERING; SMALL MOLECULE LIBRARIES; TRANSCRIPTION FACTORS; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 85006380431     PISSN: 15356108     EISSN: 18783686     Source Type: Journal    
DOI: 10.1016/j.ccell.2016.10.002     Document Type: Article

References (58)

1. Abdel-Wahab, O., Levine, R.L., Mutations in epigenetic modifiers in the pathogenesis and therapy of acute myeloid leukemia. Blood 121 (2013), 3563–3572.
2. Alayed, K., Patel, K.P., Konoplev, S., Singh, R.R., Routbort, M.J., Reddy, N., Pemmaraju, N., Zhang, L., Shaikh, A.A., Aladily, T.N., et al. TET2 mutations, myelodysplastic features, and a distinct immunoprofile characterize blastic plasmacytoid dendritic cell neoplasm in the bone marrow. Am. J. Hematol. 88 (2013), 1055–1061.
3. Assaf, C., Gellrich, S., Whittaker, S., Robson, A., Cerroni, L., Massone, C., Kerl, H., Rose, C., Chott, A., Chimenti, S., et al. CD56-positive haematological neoplasms of the skin: a multicentre study of the Cutaneous Lymphoma Project Group of the European Organisation for Research and Treatment of Cancer. J. Clin. Pathol. 60 (2007), 981–989.
4. Bailey, T.L., Boden, M., Buske, F.A., Frith, M., Grant, C.E., Clementi, L., Ren, J., Li, W.W., Noble, W.S., MEME SUITE: tools for motif discovery and searching. Nucleic Acids Res. 37 (2009), W202–W208.
5. Blasius, A.L., Arnold, C.N., Georgel, P., Rutschmann, S., Xia, Y., Lin, P., Ross, C., Li, X., Smart, N.G., Beutler, B., Slc15a4, AP-3, and Hermansky-Pudlak syndrome proteins are required for Toll-like receptor signaling in plasmacytoid dendritic cells. Proc. Natl. Acad. Sci. USA 107 (2010), 19973–19978.
6. Buenrostro, J.D., Giresi, P.G., Zaba, L.C., Chang, H.Y., Greenleaf, W.J., Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat. Methods 10 (2013), 1213–1218.
7. Bunin, A., Sisirak, V., Ghosh, H.S., Grajkowska, L.T., Hou, Z.E., Miron, M., Yang, C., Ceribelli, M., Uetani, N., Chaperot, L., et al. Protein tyrosine phosphatase PTPRS is an inhibitory receptor on human and murine plasmacytoid dendritic cells. Immunity 43 (2015), 277–288.
8. Ceribelli, M., Kelly, P.N., Shaffer, A.L., Wright, G.W., Xiao, W., Yang, Y., Mathews Griner, L.A., Guha, R., Shinn, P., Keller, J.M., et al. Blockade of oncogenic IkappaB kinase activity in diffuse large B-cell lymphoma by bromodomain and extraterminal domain protein inhibitors. Proc. Natl. Acad. Sci. USA 111 (2014), 11365–11370.
9. Chaperot, L., Bendriss, N., Manches, O., Gressin, R., Maynadie, M., Trimoreau, F., Orfeuvre, H., Corront, B., Feuillard, J., Sotto, J.J., et al. Identification of a leukemic counterpart of the plasmacytoid dendritic cells. Blood 97 (2001), 3210–3217.
10. Chaperot, L., Blum, A., Manches, O., Lui, G., Angel, J., Molens, J.P., Plumas, J., Virus or TLR agonists induce TRAIL-mediated cytotoxic activity of plasmacytoid dendritic cells. J. Immunol. 176 (2006), 248–255.
11. Chapuy, B., McKeown, M.R., Lin, C.Y., Monti, S., Roemer, M.G., Qi, J., Rahl, P.B., Sun, H.H., Yeda, K.T., Doench, J.G., et al. Discovery and characterization of super-enhancer-associated dependencies in diffuse large B cell lymphoma. Cancer Cell 24 (2013), 777–790.
12. Cisse, B., Caton, M.L., Lehner, M., Maeda, T., Scheu, S., Locksley, R., Holmberg, D., Zweier, C., den Hollander, N.S., Kant, S.G., et al. Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development. Cell 135 (2008), 37–48.
13. Colonna, M., Trinchieri, G., Liu, Y.J., Plasmacytoid dendritic cells in immunity. Nat. Immunol. 5 (2004), 1219–1226.
14. Dijkman, R., van Doorn, R., Szuhai, K., Willemze, R., Vermeer, M.H., Tensen, C.P., Gene-expression profiling and array-based CGH classify CD4+CD56+ hematodermic neoplasm and cutaneous myelomonocytic leukemia as distinct disease entities. Blood 109 (2007), 1720–1727.
15. Facchetti, F., Cigognetti, M., Fisogni, S., Rossi, G., Lonardi, S., Vermi, W., Neoplasms derived from plasmacytoid dendritic cells. Mod. Pathol. 29 (2016), 98–111.
16. Filippakopoulos, P., Qi, J., Picaud, S., Shen, Y., Smith, W.B., Fedorov, O., Morse, E.M., Keates, T., Hickman, T.T., Felletar, I., et al. Selective inhibition of BET bromodomains. Nature 468 (2010), 1067–1073.
17. Frith, M.C., Fu, Y., Yu, L., Chen, J.F., Hansen, U., Weng, Z., Detection of functional DNA motifs via statistical over-representation. Nucleic Acids Res. 32 (2004), 1372–1381.
18. Garnache-Ottou, F., Feuillard, J., Saas, P., Plasmacytoid dendritic cell leukaemia/lymphoma: towards a well defined entity?. Br. J. Haematol. 136 (2007), 539–548.
19. Garnache-Ottou, F., Feuillard, J., Ferrand, C., Biichle, S., Trimoreau, F., Seilles, E., Salaun, V., Garand, R., Lepelley, P., Maynadie, M., et al. Extended diagnostic criteria for plasmacytoid dendritic cell leukaemia. Br. J. Haematol. 145 (2009), 624–636.
20. Garraway, L.A., Sellers, W.R., Lineage dependency and lineage-survival oncogenes in human cancer. Nat. Rev. Cancer 6 (2006), 593–602.
21. Ghosh, H.S., Cisse, B., Bunin, A., Lewis, K.L., Reizis, B., Continuous expression of the transcription factor e2-2 maintains the cell fate of mature plasmacytoid dendritic cells. Immunity 33 (2010), 905–916.
22. Ghosh, H.S., Ceribelli, M., Matos, I., Lazarovici, A., Bussemaker, H.J., Lasorella, A., Hiebert, S.W., Liu, K., Staudt, L.M., Reizis, B., ETO family protein Mtg16 regulates the balance of dendritic cell subsets by repressing Id2. J. Exp. Med. 211 (2014), 1623–1635.
23. Herling, M., Teitell, M.A., Shen, R.R., Medeiros, L.J., Jones, D., TCL1 expression in plasmacytoid dendritic cells (DC2s) and the related CD4+ CD56+ blastic tumors of skin. Blood 101 (2003), 5007–5009.
24. Ippolito, G.C., Dekker, J.D., Wang, Y.H., Lee, B.K., Shaffer, A.L. 3rd, Lin, J., Wall, J.K., Lee, B.S., Staudt, L.M., Liu, Y.J., et al. Dendritic cell fate is determined by BCL11A. Proc. Natl. Acad. Sci. USA 111 (2014), E998–E1006.
25. Jang, M.K., Mochizuki, K., Zhou, M., Jeong, H.S., Brady, J.N., Ozato, K., The bromodomain protein Brd4 is a positive regulatory component of P-TEFb and stimulates RNA polymerase II-dependent transcription. Mol. Cell 19 (2005), 523–534.
26. Jardin, F., Callanan, M., Penther, D., Ruminy, P., Troussard, X., Kerckaert, J.P., Figeac, M., Parmentier, F., Rainville, V., Vaida, I., et al. Recurrent genomic aberrations combined with deletions of various tumour suppressor genes may deregulate the G1/S transition in CD4+CD56+ haematodermic neoplasms and contribute to the aggressiveness of the disease. Leukemia 23 (2009), 698–707.
27. Jardin, F., Ruminy, P., Parmentier, F., Troussard, X., Vaida, I., Stamatoullas, A., Lepretre, S., Penther, D., Duval, A.B., Picquenot, J.M., et al. TET2 and TP53 mutations are frequently observed in blastic plasmacytoid dendritic cell neoplasm. Br. J. Haematol. 153 (2011), 413–416.
28. Jaye, D.L., Geigerman, C.M., Herling, M., Eastburn, K., Waller, E.K., Jones, D., Expression of the plasmacytoid dendritic cell marker BDCA-2 supports a spectrum of maturation among CD4+ CD56+ hematodermic neoplasms. Mod. Pathol. 19 (2006), 1555–1562.
29. Julia, F., Petrella, T., Beylot-Barry, M., Bagot, M., Lipsker, D., Machet, L., Joly, P., Dereure, O., Wetterwald, M., d'Incan, M., et al. Blastic plasmacytoid dendritic cell neoplasm: clinical features in 90 patients. Br. J. Dermatol. 169 (2013), 579–586.
30. Lindstedt, M., Lundberg, K., Borrebaeck, C.A., Gene family clustering identifies functionally associated subsets of human in vivo blood and tonsillar dendritic cells. J. Immunol. 175 (2005), 4839–4846.
31. Liu, Y.J., IPC: professional type 1 interferon-producing cells and plasmacytoid dendritic cell precursors. Annu. Rev. Immunol. 23 (2005), 275–306.
32. Loven, J., Hoke, H.A., Lin, C.Y., Lau, A., Orlando, D.A., Vakoc, C.R., Bradner, J.E., Lee, T.I., Young, R.A., Selective inhibition of tumor oncogenes by disruption of super-enhancers. Cell 153 (2013), 320–334.
33. Lucioni, M., Novara, F., Fiandrino, G., Riboni, R., Fanoni, D., Arra, M., Venegoni, L., Nicola, M., Dallera, E., Arcaini, L., et al. Twenty-one cases of blastic plasmacytoid dendritic cell neoplasm: focus on biallelic locus 9p21.3 deletion. Blood 118 (2011), 4591–4594.
34. Maeda, T., Murata, K., Fukushima, T., Sugahara, K., Tsuruda, K., Anami, M., Onimaru, Y., Tsukasaki, K., Tomonaga, M., Moriuchi, R., et al. A novel plasmacytoid dendritic cell line, CAL-1, established from a patient with blastic natural killer cell lymphoma. Int. J. Hematol. 81 (2005), 148–154.
35. Marafioti, T., Paterson, J.C., Ballabio, E., Reichard, K.K., Tedoldi, S., Hollowood, K., Dictor, M., Hansmann, M.L., Pileri, S.A., Dyer, M.J., et al. Novel markers of normal and neoplastic human plasmacytoid dendritic cells. Blood 111 (2008), 3778–3792.
36. Mathews Griner, L.A., Guha, R., Shinn, P., Young, R.M., Keller, J.M., Liu, D., Goldlust, I.S., Yasgar, A., McKnight, C., Boxer, M.B., et al. High-throughput combinatorial screening identifies drugs that cooperate with ibrutinib to kill activated B-cell-like diffuse large B-cell lymphoma cells. Proc. Natl. Acad. Sci. USA 111 (2014), 2349–2354.
37. Menezes, J., Acquadro, F., Wiseman, M., Gomez-Lopez, G., Salgado, R.N., Talavera-Casanas, J.G., Buno, I., Cervera, J.V., Montes-Moreno, S., Hernandez-Rivas, J.M., et al. Exome sequencing reveals novel and recurrent mutations with clinical impact in blastic plasmacytoid dendritic cell neoplasm. Leukemia 28 (2014), 823–829.
38. Montes-Moreno, S., Ramos-Medina, R., Martinez-Lopez, A., Barrionuevo Cornejo, C., Parra Cubillos, A., Quintana-Truyenque, S., Rodriguez Pinilla, S.M., Pajares, R., Sanchez-Verde, L., Martinez-Torrecuadrada, J., et al. SPIB, a novel immunohistochemical marker for human blastic plasmacytoid dendritic cell neoplasms: characterization of its expression in major hematolymphoid neoplasms. Blood 121 (2013), 643–647.
39. Munoz, L., Nomdedeu, J.F., Lopez, O., Carnicer, M.J., Bellido, M., Aventin, A., Brunet, S., Sierra, J., Interleukin-3 receptor alpha chain (CD123) is widely expressed in hematologic malignancies. Haematologica 86 (2001), 1261–1269.
40. Nagasawa, M., Schmidlin, H., Hazekamp, M.G., Schotte, R., Blom, B., Development of human plasmacytoid dendritic cells depends on the combined action of the basic helix-loop-helix factor E2-2 and the Ets factor Spi-B. Eur. J. Immunol. 38 (2008), 2389–2400.
41. Ngo, V.N., Davis, R.E., Lamy, L., Yu, X., Zhao, H., Lenz, G., Lam, L.T., Dave, S., Yang, L., Powell, J., Staudt, L.M., A loss-of-function RNA interference screen for molecular targets in cancer. Nature 441 (2006), 106–110.
42. Pagano, L., Valentini, C.G., Pulsoni, A., Fisogni, S., Carluccio, P., Mannelli, F., Lunghi, M., Pica, G., Onida, F., Cattaneo, C., et al. Blastic plasmacytoid dendritic cell neoplasm with leukemic presentation: an Italian multicenter study. Haematologica 98 (2013), 239–246.
43. Petrella, T., Comeau, M.R., Maynadie, M., Couillault, G., De Muret, A., Maliszewski, C.R., Dalac, S., Durlach, A., Galibert, L., ‘Agranular CD4+ CD56+ hematodermic neoplasm’ (blastic NK-cell lymphoma) originates from a population of CD56+ precursor cells related to plasmacytoid monocytes. Am. J. Surg. Pathol. 26 (2002), 852–862.
44. Reizis, B., Regulation of plasmacytoid dendritic cell development. Curr. Opin. Immunol. 22 (2010), 206–211.
45. Reizis, B., Bunin, A., Ghosh, H.S., Lewis, K.L., Sisirak, V., Plasmacytoid dendritic cells: recent progress and open questions. Annu. Rev. Immunol. 29 (2011), 163–183.
46. Riaz, W., Zhang, L., Horna, P., Sokol, L., Blastic plasmacytoid dendritic cell neoplasm: update on molecular biology, diagnosis, and therapy. Cancer Control 21 (2014), 279–289.
47. Roos-Weil, D., Dietrich, S., Boumendil, A., Polge, E., Bron, D., Carreras, E., Iriondo Atienza, A., Arcese, W., Beelen, D.W., Cornelissen, J.J., et al. Stem cell transplantation can provide durable disease control in blastic plasmacytoid dendritic cell neoplasm: a retrospective study from the European Group for Blood and Marrow Transplantation. Blood 121 (2013), 440–446.
48. Rui, L., Schmitz, R., Ceribelli, M., Staudt, L.M., Malignant pirates of the immune system. Nat. Immunol. 12 (2011), 933–940.
49. Swerdlow, S.H., Campo, E., Harris, N.L., Jaffe, E.S., Pileri, S.A., Stein, H., Thiele, J., Vardiman, J.W., WHO Classification of Tumours of Haematopoietic and Lymphoid Tissue. 2008, World Health Organization.
50. Sapienza, M.R., Fuligni, F., Agostinelli, C., Tripodo, C., Righi, S., Laginestra, M.A., Pileri, A. Jr., Mancini, M., Rossi, M., Ricci, F., et al. Molecular profiling of blastic plasmacytoid dendritic cell neoplasm reveals a unique pattern and suggests selective sensitivity to NF-kB pathway inhibition. Leukemia 28 (2014), 1606–1616.
51. Sasaki, I., Hoshino, K., Sugiyama, T., Yamazaki, C., Yano, T., Iizuka, A., Hemmi, H., Tanaka, T., Saito, M., Sugiyama, M., et al. Spi-B is critical for plasmacytoid dendritic cell function and development. Blood 120 (2012), 4733–4743.
52. Sawai, C.M., Sisirak, V., Ghosh, H.S., Hou, E.Z., Ceribelli, M., Staudt, L.M., Reizis, B., Transcription factor Runx2 controls the development and migration of plasmacytoid dendritic cells. J. Exp. Med. 210 (2013), 2151–2159.
53. Schiavoni, G., Mattei, F., Sestili, P., Borghi, P., Venditti, M., Morse, H.C. 3rd, Belardelli, F., Gabriele, L., ICSBP is essential for the development of mouse type I interferon-producing cells and for the generation and activation of CD8alpha(+) dendritic cells. J. Exp. Med. 196 (2002), 1415–1425.
54. Schotte, R., Nagasawa, M., Weijer, K., Spits, H., Blom, B., The ETS transcription factor Spi-B is required for human plasmacytoid dendritic cell development. J. Exp. Med. 200 (2004), 1503–1509.
55. Shaffer, A.L., Wright, G., Yang, L., Powell, J., Ngo, V., Lamy, L., Lam, L.T., Davis, R.E., Staudt, L.M., A library of gene expression signatures to illuminate normal and pathological lymphoid biology. Immunol. Rev. 210 (2006), 67–85.
56. Spits, H., Couwenberg, F., Bakker, A.Q., Weijer, K., Uittenbogaart, C.H., Id2 and Id3 inhibit development of CD34(+) stem cells into predendritic cell (pre-DC)2 but not into pre-DC1. Evidence for a lymphoid origin of pre-DC2. J. Exp. Med. 192 (2000), 1775–1784.
57. Stenzinger, A., Endris, V., Pfarr, N., Andrulis, M., Johrens, K., Klauschen, F., Siebolts, U., Wolf, T., Koch, P.S., Schulz, M., et al. Targeted ultra-deep sequencing reveals recurrent and mutually exclusive mutations of cancer genes in blastic plasmacytoid dendritic cell neoplasm. Oncotarget 5 (2014), 6404–6413.
58. Tsujimura, H., Tamura, T., Gongora, C., Aliberti, J., Reis e Sousa, C., Sher, A., Ozato, K., ICSBP/IRF-8 retrovirus transduction rescues dendritic cell development in vitro. Blood 101 (2003), 961–969.