NF-κB deregulation in Hodgkin lymphoma

Seminars in Cancer Biology

Volumn 39, Issue , 2016, Pages 32-39

  Weniger, Marc A ^a   Küppers, Ralf ^a  

^a UNIVERSITY OF DUISBURG ESSEN   (Germany)

Author keywords

Epstein Barr virus; Hodgkin lymphoma; NF B; TNFAIP3

Indexed keywords

B CELL MATURATION ANTIGEN; CD30 ANTIGEN; CD40 ANTIGEN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; LATENT MEMBRANE PROTEIN 1; TRANSCRIPTION FACTOR;

CARCINOGENESIS; CD4+ T LYMPHOCYTE; CHROMOSOME TRANSLOCATION; CLASSICAL HODGKIN LYMPHOMA; EPSTEIN BARR VIRUS; FRAMESHIFT MUTATION; GENE DOSAGE; HODGKIN DISEASE; HUMAN; LYMPHOMA CELL LINE; MISSENSE MUTATION; MOLECULAR INTERACTION; PROTEIN ANALYSIS; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN INDUCTION; REED STERNBERG CELL; REVIEW; SIGNAL TRANSDUCTION; SOMATIC MUTATION; TUMOR MICROENVIRONMENT; EPSTEIN BARR VIRUS INFECTION; GENETICS; METABOLISM; MUTATION; PATHOLOGY; VIROLOGY;

EPSTEIN-BARR VIRUS INFECTIONS; HODGKIN DISEASE; HUMANS; MUTATION; NF-KAPPA B; SIGNAL TRANSDUCTION; TRANSCRIPTION FACTORS; TUMOR MICROENVIRONMENT;

EID: 84976475008     PISSN: 1044579X     EISSN: 10963650     Source Type: Journal    
DOI: 10.1016/j.semcancer.2016.05.001     Document Type: Review

References (103)

1. [1] Swerdlow, S.H., Campo, E., Harris, N.L., Jaffe, E.S., Pileri, S.A., Stein, H., Thiele, J., Vardiman, J.W., Classification of Tumours of Haematopoietic and Lymphoid Tissues. 2008, IARC Press, Lyon.
2. [2] Küppers, R., Engert, A., Hansmann, M.-L., Hodgkin lymphoma. J. Clin. Invest. 122 (2012), 3439–3447.
3. [3] Küppers, R., The biology of Hodgkin's lymphoma. Nat. Rev. Cancer 9 (2009), 15–27.
4. [4] Liu, Y.J., de Bouteiller, O., Fugier-Vivier, I., Mechanisms of selection and differentiation in germinal centers. Curr. Opin. Immunol. 9 (1997), 256–262.
5. [5] Basso, K., Klein, U., Niu, H., Stolovitzky, G.A., Tu, Y., Califano, A., Cattoretti, G., Dalla-Favera, R., Tracking CD40 signaling during germinal center development. Blood 104 (2004), 4088–4096.
6. [6] Bargou, R.C., Leng, C., Krappmann, D., Emmerich, F., Mapara, M.Y., Bommert, K., Royer, H.D., Scheidereit, C., Dörken, B., High-level nuclear NF-kappa B and Oct-2 is a common feature of cultured Hodgkin/Reed-Sternberg cells. Blood 87 (1996), 4340–4347.
7. [7] Gruss, H.J., Brach, M.A., Drexler, H.G., Bonifer, R., Mertelsmann, R.H., Herrmann, F., Expression of cytokine genes, cytokine receptor genes, and transcription factors in cultured Hodgkin and Reed-Sternberg cells. Cancer Res. 52 (1992), 3353–3360.
8. [8] Vallabhapurapu, S., Karin, M., Regulation and function of NF-kappaB transcription factors in the immune system. Annu. Rev. Immunol. 27 (2009), 693–733.
9. [9] Krappmann, D., Emmerich, F., Kordes, U., Scharschmidt, E., Dörken, B., Scheidereit, C., Molecular mechanisms of constitutive NF-kappaB/Rel activation in Hodgkin/Reed-Sternberg cells. Oncogene 18 (1999), 943–953.
10. [10] Mathas, S., Jöhrens, K., Joos, S., Lietz, A., Hummel, F., Janz, M., Jundt, F., Anagnostopoulos, I., Bommert, K., Lichter, P., Stein, H., Scheidereit, C., Dörken, B., Elevated NF-kappaB p50 complex formation and Bcl-3 expression in classical Hodgkin, anaplastic large-cell, and other peripheral T-cell lymphomas. Blood 106 (2005), 4287–4293.
11. [11] Wood, K.M., Roff, M., Hay, R.T., Defective IκBα in Hodgkin cell lines with constitutively active NF-κB. Oncogene 16 (1998), 2131–2139.
12. [12] Bargou, R.C., Emmerich, F., Krappmann, D., Bommert, K., Mapara, M.Y., Arnold, W., Royer, H.D., Grinstein, E., Greiner, A., Scheidereit, C., Dörken, B., Constitutive nuclear factor-kappaB-RelA activation is required for proliferation and survival of Hodgkin's disease tumor cells. J. Clin. Invest. 100 (1997), 2961–2969.
13. [13] Barth, T.F., Martin-Subero, J.I., Joos, S., Menz, C.K., Hasel, C., Mechtersheimer, G., Parwaresch, R.M., Lichter, P., Siebert, R., Mooller, P., Gains of 2p involving the REL locus correlate with nuclear c-Rel protein accumulation in neoplastic cells of classical Hodgkin lymphoma. Blood 101 (2003), 3681–3686.
14. [14] Izban, K.F., Ergin, M., Huang, Q., Qin, J., Martinez, R.L., Schnitzer, B., Ni, H., Nickoloff, B.J., Alkan, S., Characterization of NF-κB expression in Hodgkin's disease: inhibition of constitutively expressed NF-κB results in spontaneous caspase-independent apoptosis in Hodgkin and Reed-Sternberg cells. Mod. Pathol. 14 (2001), 297–310.
15. [15] Rodig, S.J., Savage, K.J., Nguyen, V., Pinkus, G.S., Shipp, M.A., Aster, J.C., Kutok, J.L., TRAF1 expression and c-Rel activation are useful adjuncts in distinguishing classical Hodgkin lymphoma from a subset of morphologically or immunophenotypically similar lymphomas. Am. J. Surg. Pathol. 29 (2005), 196–203.
16. [16] Guo, F., Sun, A., Wang, W., He, J., Hou, J., Zhou, P., Chen, Z., TRAF1 is involved in the classical NF-kappaB activation and CD30-induced alternative activity in Hodgkin's lymphoma cells. Mol. Immunol. 46 (2009), 2441–2448.
17. [17] Nonaka, M., Horie, R., Itoh, K., Watanabe, T., Yamamoto, N., Yamaoka, S., Aberrant NF-kappaB2/p52 expression in Hodgkin/Reed-Sternberg cells and CD30-transformed rat fibroblasts. Oncogene 24 (2005), 3976–3986.
18. [18] Brune, V., Tiacci, E., Pfeil, I., Döring, C., Eckerle, S., van Noesel, C.J.M., Klapper, W., Falini, B., von Heydebreck, A., Metzler, D., Bräuninger, A., Hansmann, M.-L., Küppers, R., Origin and pathogenesis of nodular lymphocyte-predominant Hodgkin lymphoma as revealed by global gene expression analysis. J. Exp. Med. 205 (2008), 2251–2268.
19. [19] de Oliveira, K.A.P., Kaergel, E., Heinig, M., Fontaine, J.-F., Patone, G., Muro, E.M., Mathas, S., Hummel, M., Andrade-Navarro, M.A., Hübner, N., Scheidereit, C., A roadmap of constitutive NF-kB activity in Hodgkin lymphoma: dominant roles of p50 and p52 revealed by genome-wide analyses. Genome Med., 8, 2016 28.
20. [20] Ranuncolo, S.M., Pittaluga, S., Evbuomwan, M.O., Jaffe, E.S., Lewis, B.A., Hodgkin lymphoma requires stabilized NIK and constitutive RelB expression for survival. Blood 120 (2012), 3756–3763.
21. [21] Saitoh, Y., Yamamoto, N., Dewan, M.Z., Sugimoto, H., Martinez Bruyn, V.J., Iwasaki, Y., Matsubara, K., Qi, X., Saitoh, T., Imoto, I., Inazawa, J., Utsunomiya, A., Watanabe, T., Masuda, T., Yamamoto, N., Yamaoka, S., Overexpressed NF-kappaB-inducing kinase contributes to the tumorigenesis of adult T-cell leukemia and Hodgkin Reed-Sternberg cells. Blood 111 (2008), 5118–5129.
22. [22] Hinz, M., Loser, P., Mathas, S., Krappmann, D., Dorken, B., Scheidereit, C., Constitutive NF-kappaB maintains high expression of a characteristic gene network, including CD40, CD86, and a set of antiapoptotic genes in Hodgkin/Reed-Sternberg cells. Blood 97 (2001), 2798–2807.
23. [23] Hinz, M., Lemke, P., Anagnostopoulos, I., Hacker, C., Krappmann, D., Mathas, S., Dörken, B., Zenke, M., Stein, H., Scheidereit, C., Nuclear factor kappaB-dependent gene expression profiling of Hodgkin's disease tumor cells, pathogenetic significance, and link to constitutive signal transducer and activator of transcription 5a activity. J. Exp. Med. 196 (2002), 605–617.
24. [24] Höpken, U.E., Foss, H.D., Meyer, D., Hinz, M., Leder, K., Stein, H., Lipp, M., Up-regulation of the chemokine receptor CCR7 in classical but not in lymphocyte-predominant Hodgkin disease correlates with distinct dissemination of neoplastic cells in lymphoid organs. Blood 99 (2002), 1109–1116.
25. [25] Schwering, I., Bräuninger, A., Klein, U., Jungnickel, B., Tinguely, M., Diehl, V., Hansmann, M.L., Dalla-Favera, R., Rajewsky, K., Küppers, R., Loss of the B-lineage-specific gene expression program in Hodgkin and Reed-Sternberg cells of Hodgkin lymphoma. Blood 101 (2003), 1505–1512.
26. [26] Steidl, C., Connors, J.M., Gascoyne, R.D., Molecular pathogenesis of Hodgkin's lymphoma: increasing evidence of the importance of the microenvironment. J. Clin. Oncol. 29 (2011), 1812–1826.
27. [27] Wein, F., Otto, T., Lambertz, P., Fandrey, J., Hansmann, M.L., Küppers, R., Potential role of hypoxia in early stages of Hodgkin lymphoma pathogenesis. Haematologica 100 (2015), 1320–1326.
28. [28] Molin, D., Fischer, M., Xiang, Z., Larsson, U., Harvima, I., Venge, P., Nilsson, K., Sundstrom, C., Enblad, G., Nilsson, G., Mast cells express functional CD30 ligand and are the predominant CD30L-positive cells in Hodgkin's disease. Br. J. Haematol. 114 (2001), 616–623.
29. [29] Pinto, A., Aldinucci, D., Gloghini, A., Zagonel, V., Degan, M., Improta, S., Juzbasic, S., Todesco, M., Perin, V., Gattei, V., Herrmann, F., Gruss, H.J., Carbone, A., Human eosinophils express functional CD30 ligand and stimulate proliferation of a Hodgkin's disease cell line. Blood 88 (1996), 3299–3305.
30. [30] Hansen, H.P., Engels, H.M., Dams, M., Paes Leme, A.F., Pauletti, B.A., Simhadri, V.L., Dürkop, H., Reiners, K.S., Barnert, S., Engert, A., Schubert, R., Quondamatteo, F., Hallek, M., Pogge von Strandmann, E., Protrusion-guided extracellular vesicles mediate CD30 trans-signalling in the microenvironment of Hodgkin's lymphoma. J. Pathol. 232 (2014), 405–414.
31. [31] Horie, R., Watanabe, T., Ito, K., Morisita, Y., Watanabe, M., Ishida, T., Higashihara, M., Kadin, M., Watanabe, T., Cytoplasmic aggregation of TRAF2 and TRAF5 proteins in the Hodgkin-Reed-Sternberg cells. Am. J. Pathol. 160 (2002), 1647–1654.
32. [32] Mir, S.S., Richter, B.W., Duckett, C.S., Differential effects of CD30 activation in anaplastic large cell lymphoma and Hodgkin disease cells. Blood 96 (2000), 4307–4312.
33. [33] Wright, C.W., Rumble, J.M., Duckett, C.S., CD30 activates both the canonical and alternative NF-kappaB pathways in anaplastic large cell lymphoma cells. J. Biol. Chem. 282 (2007), 10252–10262.
34. [34] Hirsch, B., Hummel, M., Bentink, S., Fouladi, F., Spang, R., Zollinger, R., Stein, H., Dürkop, H., CD30-induced signaling is absent in Hodgkin's cells but present in anaplastic large cell lymphoma cells. Am. J. Pathol. 172 (2008), 510–520.
35. [35] Carbone, A., Gloghini, A., Gattei, V., Aldinucci, D., Degan, M., De Paoli, P., Zagonel, V., Pinto, A., Expression of functional CD40 antigen on Reed-Sternberg cells and Hodgkin's disease cell lines. Blood 85 (1995), 780–789.
36. [36] O'Grady, J.T., Stewart, S., Lowrey, J., Howie, S.E., Krajewski, A.S., CD40 expression in Hodgkin's disease. Am. J. Pathol. 144 (1994), 21–26.
37. [37] Carbone, A., Gloghini, A., Gruss, H.J., Pinto, A., CD40 ligand is constitutively expressed in a subset of T cell lymphomas and on the microenvironmental reactive T cells of follicular lymphomas and Hodgkin's disease. Am. J. Pathol. 147 (1995), 912–922.
38. [38] Annunziata, C.M., Safiran, Y.J., Irving, S.G., Kasid, U.N., Cossman, J., Hodgkin disease: pharmacologic intervention of the CD40-NF kappa B pathway by a protease inhibitor. Blood 96 (2000), 2841–2848.
39. [39] Chiu, A., Xu, W., He, B., Dillon, S.R., Gross, J.A., Sievers, E., Qiao, X., Santini, P., Hyjek, E., Lee, J.W., Cesarman, E., Chadburn, A., Knowles, D.M., Cerutti, A., Hodgkin lymphoma cells express TACI and BCMA receptors and generate survival and proliferation signals in response to BAFF and APRIL. Blood 109 (2007), 729–739.
40. [40] Schwaller, J., Went, P., Matthes, T., Dirnhofer, S., Donze, O., Mhawech-Fauceglia, P., Myit, S., Huard, B., Paracrine promotion of tumor development by the TNF ligand APRIL in Hodgkin's disease. Leukemia 21 (2007), 1324–1327.
41. [41] Theill, L.E., Boyle, W.J., Penninger, J.M., RANK-L and RANK: T cells, bone loss, and mammalian evolution. Annu. Rev. Immunol. 20 (2002), 795–823.
42. [42] Fiumara, P., Snell, V., Li, Y., Mukhopadhyay, A., Younes, M., Gillenwater, A.M., Cabanillas, F., Aggarwal, B.B., Younes, A., Functional expression of receptor activator of nuclear factor kappaB in Hodgkin disease cell lines. Blood 98 (2001), 2784–2790.
43. [43] Rodig, S.J., Shahsafaei, A., Li, B., Mackay, C.R., Dorfman, D.M., BAFF-R, the major B cell-activating factor receptor, is expressed on most mature B cells and B-cell lymphoproliferative disorders. Hum. Pathol. 36 (2005), 1113–1119.
44. [44] Cabannes, E., Khan, G., Aillet, F., Jarrett, R.F., Hay, R.T., Mutations in the IκBα gene in Hodgkin's disease suggest a tumour suppressor role for IκBα. Oncogene 18 (1999), 3063–3070.
45. [45] Emmerich, F., Meiser, M., Hummel, M., Demel, G., Foss, H.D., Jundt, F., Mathas, S., Krappmann, D., Scheidereit, C., Stein, H., Dörken, B., Overexpression of I kappa B alpha without inhibition of NF-kappaB activity and mutations in the I kappa B alpha gene in Reed-Sternberg cells. Blood 94 (1999), 3129–3134.
46. [46] Emmerich, F., Theurich, S., Hummel, M., Haeffker, A., Vry, M.S., Döhner, K., Bommert, K., Stein, H., Dörken, B., Inactivating I kappa B epsilon mutations in Hodgkin/Reed-Sternberg cells. J. Pathol. 201 (2003), 413–420.
47. [47] Jungnickel, B., Staratschek-Jox, A., Bräuninger, A., Spieker, T., Wolf, J., Diehl, V., Hansmann, M.-L., Rajewsky, K., Küppers, R., Clonal deleterious mutations in the IkBa gene in the malignant cells in Hodgkin's disease. J. Exp. Med. 191 (2000), 395–401.
48. [48] Kato, M., Sanada, M., Kato, I., Sato, Y., Takita, J., Takeuchi, K., Niwa, A., Chen, Y., Nakazaki, K., Nomoto, J., Asakura, Y., Muto, S., Tamura, A., Iio, M., Akatsuka, Y., Hayashi, Y., Mori, H., Igarashi, T., Kurokawa, M., Chiba, S., Mori, S., Ishikawa, Y., Okamoto, K., Tobinai, K., Nakagama, H., Nakahata, T., Yoshino, T., Kobayashi, Y., Ogawa, S., Frequent inactivation of A20 in B-cell lymphomas. Nature 459 (2009), 712–716.
49. [49] Nomoto, J., Hiramoto, N., Kato, M., Sanada, M., Maeshima, A.M., Taniguchi, H., Hosoda, F., Asakura, Y., Munakata, W., Sekiguchi, N., Maruyama, D., Watanabe, T., Nakagama, H., Takeuchi, K., Tobinai, K., Ogawa, S., Kobayashi, Y., Deletion of the TNFAIP3/A20 gene detected by FICTION analysis in classical Hodgkin lymphoma. BMC Cancer, 12, 2012, 457.
50. [50] Schmitz, R., Hansmann, M.L., Bohle, V., Martin-Subero, J.I., Hartmann, S., Mechtersheimer, G., Klapper, W., Vater, I., Giefing, M., Gesk, S., Stanelle, J., Siebert, R., Küppers, R., TNFAIP3 (A20) is a tumor suppressor gene in Hodgkin lymphoma and primary mediastinal B cell lymphoma. J. Exp. Med. 206 (2009), 981–989.
51. [51] Liu, X., Yu, H., Yang, W., Zhou, X., Lu, H., Shi, D., Mutations of NFKBIA in biopsy specimens from Hodgkin lymphoma. Cancer Genet. Cytogenet. 197 (2010), 152–157.
52. [52] Schmidt, A., Schmitz, R., Giefing, M., Martin-Subero, J.I., Gesk, S., Vater, I., Massow, A., Maggio, E., Schneider, M., Hansmann, M.L., Siebert, R., Küppers, R., Rare occurrence of biallelic CYLD gene mutations in classical Hodgkin lymphoma. Genes. Chromosomes Cancer 49 (2010), 803–809.
53. [53] Lake, A., Shield, L.A., Cordano, P., Chui, D.T., Osborne, J., Crae, S., Wilson, K.S., Tosi, S., Knight, S.J., Gesk, S., Siebert, R., Hay, R.T., Jarrett, R.F., Mutations of NFKBIA, encoding IkappaBalpha, are a recurrent finding in classical Hodgkin lymphoma but are not a unifying feature of non-EBV-associated cases. Int. J. Cancer 125 (2009), 1334–1342.
54. [54] Ohshima, K., Haraoka, S., Yoshioka, S., Kawasaki, C., Tutiya, T., Suzumiya, J., Kikuchi, M., Chromosome 16q deletion and loss of E-cadherin expression in Hodgkin and Reed-Sternberg cells. Int. J. Cancer 92 (2001), 678–682.
55. [55] Otto, C., Giefing, M., Massow, A., Vater, I., Gesk, S., Schlesner, M., Richter, J., Klapper, W., Hansmann, M.-L., Siebert, R., Küppers, R., Genetic lesions of the TRAF3 and MAP3K14 genes in classical Hodgkin lymphoma. Br. J. Haematol. 157 (2012), 702–708.
56. [56] Joos, S., Menz, C.K., Wrobel, G., Siebert, R., Gesk, S., Ohl, S., Mechtersheimer, G., Trümper, L., Möller, P., Lichter, P., Barth, T.F., Classical Hodgkin lymphoma is characterized by recurrent copy number gains of the short arm of chromosome 2. Blood 99 (2002), 1381–1387.
57. [57] Martin-Subero, J.I., Gesk, S., Harder, L., Sonoki, T., Tucker, P.W., Schlegelberger, B., Grote, W., Novo, F.J., Calasanz, M.J., Hansmann, M.L., Dyer, M.J., Siebert, R., Recurrent involvement of the REL and BCL11A loci in classical Hodgkin lymphoma. Blood 99 (2002), 1474–1477.
58. [58] Steidl, C., Telenius, A., Shah, S.P., Farinha, P., Barclay, L., Boyle, M., Connors, J.M., Horsman, D.E., Gascoyne, R.D., Genome-wide copy number analysis of Hodgkin Reed-Sternberg cells identifies recurrent imbalances with correlations to treatment outcome. Blood 116 (2010), 418–427.
59. [59] Hartmann, S., Martin-Subero, J.I., Gesk, S., Husken, J., Giefing, M., Nagel, I., Riemke, J., Chott, A., Klapper, W., Parrens, M., Merlio, J.P., Küppers, R., Bräuninger, A., Siebert, R., Hansmann, M.L., Detection of genomic imbalances in microdissected Hodgkin and Reed-Sternberg cells of classical Hodgkin's lymphoma by array-based comparative genomic hybridization. Haematologica 93 (2008), 1318–1326.
60. [60] Enciso-Mora, V., Broderick, P., Ma, Y., Jarrett, R.F., Hjalgrim, H., Hemminki, K., van den Berg, A., Olver, B., Lloyd, A., Dobbins, S.E., Lightfoot, T., van Leeuwen, F.E., Forsti, A., Diepstra, A., Broeks, A., Vijayakrishnan, J., Shield, L., Lake, A., Montgomery, D., Roman, E., Engert, A., von Strandmann, E.P., Reiners, K.S., Nolte, I.M., Smedby, K.E., Adami, H.O., Russell, N.S., Glimelius, B., Hamilton-Dutoit, S., de Bruin, M., Ryder, L.P., Molin, D., Sorensen, K.M., Chang, E.T., Taylor, M., Cooke, R., Hofstra, R., Westers, H., van Wezel, T., van Eijk, R., Ashworth, A., Rostgaard, K., Melbye, M., Swerdlow, A.J., Houlston, R.S., A genome-wide association study of Hodgkin's lymphoma identifies new susceptibility loci at 2p16.1 (REL), 8q24.21 and 10p14 (GATA3). Nat. Genet. 42 (2010), 1126–1130.
61. [61] Martin-Subero, J.I., Wlodarska, I., Bastard, C., Picquenot, J.M., Höppner, J., Giefing, M., Klapper, W., Siebert, R., Chromosomal rearrangements involving the BCL3 locus are recurrent in classical Hodgkin and peripheral T-cell lymphoma. Blood 108 (2006), 401–402.
62. [62] Szymanowska, N., Klapper, W., Gesk, S., Küppers, R., Martin-Subero, J.I., Siebert, R., BCL2 and BCL3 are recurrent translocation partners of the IGH locus. Cancer Genet. Cytogenet. 186 (2008), 110–114.
63. [63] Joos, S., Granzow, M., Holtgreve-Grez, H., Siebert, R., Harder, L., Martin-Subero, J.I., Wolf, J., Adamowicz, M., Barth, T.F., Lichter, P., Jauch, A., Hodgkin's lymphoma cell lines are characterized by frequent aberrations on chromosomes 2p and 9p including REL and JAK2. Int. J. Cancer 103 (2003), 489–495.
64. [64] Salipante, S.J., Adey, A., Thomas, A., Lee, C., Liu, Y.J., Kumar, A., Lewis, A.P., Wu, D., Fromm, J.R., Shendure, J., Recurrent somatic loss of TNFRSF14 in classical Hodgkin lymphoma. Genes. Chromosomes Cancer, 55, 2016, 2015 early online Dec 9.
65. [65] Cheung, K.J., Johnson, N.A., Affleck, J.G., Severson, T., Steidl, C., Ben-Neriah, S., Schein, J., Morin, R.D., Moore, R., Shah, S.P., Qian, H., Paul, J.E., Telenius, A., Relander, T., Lam, W., Savage, K., Connors, J.M., Brown, C., Marra, M.A., Gascoyne, R.D., Horsman, D.E., Acquired TNFRSF14 mutations in follicular lymphoma are associated with worse prognosis. Cancer Res. 70 (2010), 9166–9174.
66. [66] Lohr, J.G., Stojanov, P., Lawrence, M.S., Auclair, D., Chapuy, B., Sougnez, C., Cruz-Gordillo, P., Knoechel, B., Asmann, Y.W., Slager, S.L., Novak, A.J., Dogan, A., Ansell, S.M., Link, B.K., Zou, L., Gould, J., Saksena, G., Stransky, N., Rangel-Escareno, C., Fernandez-Lopez, J.C., Hidalgo-Miranda, A., Melendez-Zajgla, J., Hernandez-Lemus, E., Schwarz-Cruz y Celis, A., Imaz-Rosshandler, I., Ojesina, A.I., Jung, J., Pedamallu, C.S., Lander, E.S., Habermann, T.M., Cerhan, J.R., Shipp, M.A., Getz, G., Golub, T.R., Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing. Proc. Natl. Acad. Sci. U. S. A. 109 (2012), 3879–3884.
67. [67] Bechill, J., Muller, W.J., Herpesvirus entry mediator (HVEM) attenuates signals mediated by the lymphotoxin beta receptor (LTbetaR) in human cells stimulated by the shared ligand LIGHT. Mol. Immunol. 62 (2014), 96–103.
68. [68] Schumacher, M.A., Schmitz, R., Brune, V., Tiacci, E., Döring, C., Hansmann, M.L., Siebert, R., Küppers, R., Mutations in the genes coding for the NF-kappaB regulating factors IkappaBalpha and A20 are uncommon in nodular lymphocyte-predominant Hodgkin's lymphoma. Haematologica 95 (2010), 153–157.
69. [69] Hartmann, S., Döring, C., Vucic, E., Chan, F.C., Ennishi, D., Tousseyn, T., de Wolf-Peeters, C., Perner, S., Wlodarska, I., Steidl, C., Gascoyne, R.D., Hansmann, M.L., Array comparative genomic hybridization reveals similarities between nodular lymphocyte predominant Hodgkin lymphoma and T cell/histiocyte rich large B cell lymphoma. Br. J. Haematol. 169 (2015), 415–422.
70. [70] Anagnostopoulos, I., Herbst, H., Niedobitek, G., Stein, H., Demonstration of monoclonal EBV genomes in Hodgkin's disease and Ki-1- positive anaplastic large cell lymphoma by combined Southern blot and in situ hybridization. Blood 74 (1989), 810–816.
71. [71] Caldwell, R.G., Wilson, J.B., Anderson, S.J., Longnecker, R., Epstein-Barr virus LMP2A drives B cell development and survival in the absence of normal B cell receptor signals. Immunity 9 (1998), 405–411.
72. [72] Huen, D.S., Henderson, S.A., Croom-Carter, D., Rowe, M., The Epstein-Barr virus latent membrane protein-1 (LMP1) mediates activation of NF-kappa B and cell surface phenotype via two effector regions in its carboxy-terminal cytoplasmic domain. Oncogene 10 (1995), 549–560.
73. [73] Kilger, E., Kieser, A., Baumann, M., Hammerschmidt, W., Epstein-Barr virus-mediated B-cell proliferation is dependent upon latent membrane protein 1, which simulates an activated CD40 receptor. EMBO J. 17 (1998), 1700–1709.
74. [74] Küppers, R., Rajewsky, K., The origin of Hodgkin and Reed/Sternberg cells in Hodgkin's disease. Annu. Rev. Immunol. 16 (1998), 471–493.
75. [75] Bechtel, D., Kurth, J., Unkel, C., Küppers, R., Transformation of BCR-deficient germinal-center B cells by EBV supports a major role of the virus in the pathogenesis of Hodgkin and posttransplantation lymphomas. Blood 106 (2005), 4345–4350.
76. [76] Mancao, C., Altmann, M., Jungnickel, B., Hammerschmidt, W., Rescue of crippled germinal center B cells from apoptosis by Epstein-Barr virus. Blood 106 (2005), 4339–4344.
77. [77] Chaganti, S., Bell, A.I., Begue-Pastor, N., Milner, A.E., Drayson, M., Gordon, J., Rickinson, A.B., Epstein-Barr virus infection in vitro can resue germinal centre B cells with inactivated immunoglobulin genes. Blood 106 (2005), 4249–4252.
78. [78] Küppers, R., B cells under influence: transformation of B cells by Epstein-Barr virus. Nat. Rev. Immunol. 3 (2003), 801–812.
79. [79] Bräuninger, A., Schmitz, R., Bechtel, D., Renné, C., Hansmann, M.-L., Küppers, R., Molecular biology of Hodgkin and Reed/Sternberg cells in Hodgkin's lymphoma. Int. J. Cancer 118 (2006), 1853–1861.
80. [80] Mancao, C., Hammerschmidt, W., Epstein-Barr virus latent membrane protein 2A is a B-cell receptor mimic and essential for B-cell survival. Blood 110 (2007), 3715–3721.
81. [81] Hacker, H., Tseng, P.H., Karin, M., Expanding TRAF function: TRAF3 as a tri-faced immune regulator. Nat. Rev. Immunol. 11 (2011), 457–468.
82. [82] Gallagher, E., Enzler, T., Matsuzawa, A., Anzelon-Mills, A., Otero, D., Holzer, R., Janssen, E., Gao, M., Karin, M., Kinase MEKK1 is required for CD40-dependent activation of the kinases Jnk and p38, germinal center formation, B cell proliferation and antibody production. Nat. Immunol. 8 (2007), 57–63.
83. [83] Zheng, B., Fiumara, P., Li, Y.V., Georgakis, G., Snell, V., Younes, M., Vauthey, J.N., Carbone, A., Younes, A., MEK/ERK pathway is aberrantly active in Hodgkin disease: a signaling pathway shared by CD30, CD40, and RANK that regulates cell proliferation and survival. Blood 102 (2003), 1019–1027.
84. [84] Mathas, S., Hinz, M., Anagnostopoulos, I., Krappmann, D., Lietz, A., Jundt, F., Bommert, K., Mechta-Grigoriou, F., Stein, H., Dörken, B., Scheidereit, C., Aberrantly expressed c-Jun and JunB are a hallmark of Hodgkin lymphoma cells, stimulate proliferation and synergize with NF-kappa B. EMBO J. 21 (2002), 4104–4113.
85. [85] Watanabe, M., Sasaki, M., Itoh, K., Higashihara, M., Umezawa, K., Kadin, M.E., Abraham, L.J., Watanabe, T., Horie, R., JunB induced by constitutive CD30-extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase signaling activates the CD30 promoter in anaplastic large cell lymphoma and reed-sternberg cells of Hodgkin lymphoma. Cancer Res. 65 (2005), 7628–7634.
86. [86] Leventaki, V., Drakos, E., Karanikou, M., Psatha, K., Lin, P., Schlette, E., Eliopoulos, A., Vassilakopoulos, T.P., Papadaki, H., Patsouris, E., Medeiros, L.J., Rassidakis, G.Z., c-JUN N-terminal kinase (JNK) is activated and contributes to tumor cell proliferation in classical Hodgkin lymphoma. Hum. Pathol. 45 (2014), 565–572.
87. [87] Drakos, E., Leventaki, V., Schlette, E.J., Jones, D., Lin, P., Medeiros, L.J., Rassidakis, G.Z., c-Jun expression and activation are restricted to CD30+ lymphoproliferative disorders. Am. J. Surg. Pathol. 31 (2007), 447–453.
88. [88] Mukhopadhyay, A., Fiumara, P., Li, Y., Darnay, B.G., Aggrawal, B., Younes, A., Receptor activator of nuclear factor-kB ligand activates mitogen-activated protein kinases signaling pathways in hodgki and reed-Sternberg cells. Blood 99 (2002), 3485–3486.
89. [89] Fernandez, M., Manso, R., Bernaldo de Quiros, F., Lopez, P., Martin-Duce, A., Alemany, S., Involvement of Cot activity in the proliferation of ALCL lymphoma cells. Biochem. Biophys. Res. Commun. 411 (2011), 655–660.
90. [90] Eliopoulos, A.G., Davies, C., Blake, S.S., Murray, P., Najafipour, S., Tsichlis, P.N., Young, L.S., The oncogenic protein kinase Tpl-2/Cot contributes to Epstein-Barr virus-encoded latent infection membrane protein 1-induced NF-kappaB signaling downstream of TRAF2. J. Virol. 76 (2002), 4567–4579.
91. [91] Stanelle, J., Döring, C., Hansmann, M.L., Küppers, R., Mechanisms of aberrant GATA3 expression in classical Hodgkin lymphoma and its consequences for the cytokine profile of Hodgkin and Reed/Sternberg cells. Blood 116 (2010), 4202–4211.
92. [92] Schwarzer, R., Dörken, B., Jundt, F., Notch is an essential upstream regulator of NF-kappaB and is relevant for survival of Hodgkin and Reed-Sternberg cells. Leukemia 26 (2012), 806–813.
93. [93] Lim, K.H., Yang, Y., Staudt, L.M., Pathogenetic importance and therapeutic implications of NF-kappaB in lymphoid malignancies. Immunol. Rev. 246 (2012), 359–378.
94. [94] Seifert, M., Scholtysik, R., Kuppers, R., Origin and pathogenesis of B cell lymphomas. Methods Mol. Biol. 971 (2013), 1–25.
95. [95] Ushmorov, A., Leithäuser, F., Sakk, O., Weinhausel, A., Popov, S.W., Möller, P., Wirth, T., Epigenetic processes play a major role in B-cell-specific gene silencing in classical Hodgkin lymphoma. Blood 107 (2006), 2493–2500.
96. [96] Reichel, J., Chadburn, A., Rubinstein, P.G., Giulino-Roth, L., Tam, W., Liu, Y., Gaiolla, R., Eng, K., Brody, J., Inghirami, G., Carlo-Stella, C., Santoro, A., Rahal, D., Totonchy, J., Elemento, O., Cesarman, E., Roshal, M., Flow-sorting and exome sequencing reveals the oncogenome of primary Hodgkin and Reed-Sternberg cells. Blood 125 (2015), 1061–1072.
97. [97] Martin-Subero, J.I., Knippschild, U., Harder, L., Barth, T.F., Riemke, J., Grohmann, S., Gesk, S., Hoppner, J., Moller, P., Parwaresch, R.M., Siebert, R., Segmental chromosomal aberrations and centrosome amplifications: pathogenetic mechanisms in Hodgkin and Reed-Sternberg cells of classical Hodgkin's lymphoma?. Leukemia 17 (2003), 2214–2219.
98. [98] Vockerodt, M., Belge, G., Kube, D., Irsch, J., Siebert, R., Tesch, H., Diehl, V., Wolf, J., Bullerdiek, J., Staratschek-Jox, A., An unbalanced translocation involving chromosome 14 is the probable cause for loss of potentially functional rearranged immunoglobulin heavy chain genes in the Epstein-Barr virus-positive Hodgkin's lymphoma-derived cell line L591. Br. J. Haematol. 119 (2002), 640–646.
99. [99] Kanzler, H., Hansmann, M.L., Kapp, U., Wolf, J., Diehl, V., Rajewsky, K., Küppers, R., Molecular single cell analysis demonstrates the derivation of a peripheral blood-derived cell line (L1236) from the Hodgkin/Reed-Sternberg cells of a Hodgkin's lymphoma patient. Blood 87 (1996), 3429–3436.
100. [100] Feys, T., Poppe, B., De Preter, K., Van Roy, N., Verhasselt, B., De Paepe, P., De Paepe, A., Speleman, F., A detailed inventory of DNA copy number alterations in four commonly used Hodgkin's lymphoma cell lines. Haematologica 92 (2007), 913–920.
101. [101] Scholtysik, R., Nagel, I., Kreuz, M., Vater, I., Giefing, M., Schwaenen, C., Wessendorf, S., Trümper, L., Loeffler, M., Siebert, R., Küppers, R., Recurrent deletions of the TNFSF7 and TNFSF9 genes in 19p13.3 in diffuse large B-cell and Burkitt lymphomas. Int. J. Cancer 131 (2012), E830–835.
102. [102] Giefing, M., Arnemann, J., Martin-Subero, J.I., Nielander, I., Bug, S., Hartmann, S., Arnold, N., Tiacci, E., Frank, M., Hansmann, M.L., Küppers, R., Siebert, R., Identification of candidate tumour suppressor gene loci for Hodgkin and Reed-Sternberg cells by characterisation of homozygous deletions in classical Hodgkin lymphoma cell lines. Br. J. Haematol. 142 (2008), 916–924.
103. [103] Küppers R., 2011, Biology of Hodgkin's lymphoma. Hematology Education: the education programme for the annual congress of the European Hematology Association 5, 151-157.