Epstein Barr Virus Volume 1 pp 315-337

Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 390)

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The Role of EBV in the Pathogenesis of Diffuse Large B Cell Lymphoma

Chapter

Abstract

Epstein-Barr virus (EBV) infection is a common feature of B cell lymphoproliferative disorders (LPDs), including diffuse large B cell lymphoma. Approximately 10 % of DLBCLs are EBV-positive, with the highest incidence in immunocompromised and elderly patients. Here, we review the clinical, genetic, and pathologic characteristics of DLBCL and discuss the molecular role of EBV in lymphoma tumorigenesis. Using EBV-positive DLBCL of the elderly as a model, we describe the key features of EBV-positive DLBCL. Studies of EBV-positive DLBCL of the elderly demonstrate that EBV-positive DLBCL has a distinct biology, related to both viral and host factors. The pathogenic mechanisms noted in EBV-positive DLBCL of the elderly, including enhanced NFκB activity, are likely to be a generalizable feature of EBV-positive DLBCL. Therefore, we review how this information might be used to target the EBV or its host response for the development of novel treatment strategies.

References

  1. Addis B, Isaacson P (1986) Large cell lymphoma of the mediastinum: a B-cell tumour of probable thymic origin. Histopathology 10:379–390PubMedCrossRefGoogle Scholar
  2. Al-Humood S, Alqallaf A, Al-Shemmari S, Al-Faris L, Al-Ayadhy B (2014) Genetic and immunohistochemical characterization of Epstein-Barr virus-associated diffuse large B-cell lymphoma. Acta Haematol 131:1–10PubMedCrossRefGoogle Scholar
  3. Alizadeh AA et al (2000) Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 403:503–511PubMedCrossRefGoogle Scholar
  4. Ao Q, Wang Y, Xu S, Tian Y, Huang W (2014) A case of EBV positive diffuse large B-cell lymphoma of the adolescent. Int J Clin Exp Med 7:307–311PubMedCentralPubMedGoogle Scholar
  5. Balague Ponz O et al (2009) Commentary on the WHO classification of tumors of lymphoid tissues (2008): aggressive B-cell lymphomas. J Hematop 2:83–87Google Scholar
  6. Bayerdörffer E et al (1995) Regression of primary gastric lymphoma of mucosa-associated lymphoid tissue type after cure of Helicobacter pylori infection. The Lancet 345:1591–1594CrossRefGoogle Scholar
  7. Bea S et al (2005) Diffuse large B-cell lymphoma subgroups have distinct genetic profiles that influence tumor biology and improve gene-expression-based survival prediction. Blood 106:3183–3190PubMedCentralPubMedCrossRefGoogle Scholar
  8. Béguelin W et al (2013) EZH2 is required for germinal center formation and somatic EZH2 mutations promote lymphoid transformation. Cancer Cell 23:677–692PubMedCentralPubMedCrossRefGoogle Scholar
  9. Beltran BE et al (2011a) EBV-positive diffuse large B-cell lymphoma in young immunocompetent individuals. Clin Lymphoma Myeloma Leuk 11:512–516PubMedCrossRefGoogle Scholar
  10. Beltran BE et al (2011b) EBV-positive diffuse large B-cell lymphoma of the elderly: a case series from Peru. Am J Hematol 86:663–667PubMedCrossRefGoogle Scholar
  11. Capello D et al (2010) Genome wide DNA-profiling of HIV-related B-cell lymphomas. Br J Haematol 148:245–255PubMedCrossRefGoogle Scholar
  12. Carbone A, Gloghini A (2005) AIDS-related lymphomas: from pathogenesis to pathology. Br J Haematol 130:662–670PubMedCrossRefGoogle Scholar
  13. Carel J, Myones B, Frazier B, Holers VM (1990) Structural requirements for C3d, g/Epstein-Barr virus receptor (CR2/CD21) ligand binding, internalization, and viral infection. J Biol Chem 265:12293–12299PubMedGoogle Scholar
  14. Castillo J, Pantanowitz L, Dezube BJ (2008) HIV-associated plasmablastic lymphoma: Lessons learned from 112 published cases. Am J Hematol 83:804–809PubMedCrossRefGoogle Scholar
  15. Castillo JJ et al (2011) Epstein-barr virus-positive diffuse large B-cell lymphoma of the elderly: what we know so far. Oncologist 16:87–96PubMedCentralPubMedCrossRefGoogle Scholar
  16. Cazals-Hatem D et al (1996) Primary mediastinal large B-cell lymphoma: A clinicopathologic study of 141 cases compared with 916 nonmediastinal large B-cell lymphomas, a GELA (“Groupe d’Etude des Lymphomes de l’Adulte”) study. Am J Surg Pathol 20:877–888PubMedCrossRefGoogle Scholar
  17. Chang KL, Chen Y-Y, Shibata D, Weiss LM (1992) Description of an in situ hybridization methodology for detection of Epstein-Barr virus RNA in paraffin-embedded tissues, with a survey of normal and neoplastic tissues. Diagn Mol Pathol 1:246–255PubMedCrossRefGoogle Scholar
  18. Chang ST et al (2014) Epstein-Barr virus is rarely associated with diffuse large B cell lymphoma in Taiwan and carries a trend for a shorter median survival time. J Clin Pathol 67:326–332PubMedCrossRefGoogle Scholar
  19. Cho EY et al (2008) The spectrum of Epstein-Barr virus-associated lymphoproliferative disease in Korea: incidence of disease entities by age groups. J Korean Med Sci 23:185–192PubMedCentralPubMedCrossRefGoogle Scholar
  20. Choi WW et al (2009) A new immunostain algorithm classifies diffuse large B-cell lymphoma into molecular subtypes with high accuracy. Clin Cancer Res Off J Am Assoc Cancer Res 15:5494–5502CrossRefGoogle Scholar
  21. Cohen M et al (2014) Epstein-Barr virus-positive diffuse large B-cell lymphoma association is not only restricted to elderly patients. Int J CancerGoogle Scholar
  22. Corti M et al (2010) AIDS related lymphomas: histopathological subtypes and association with Epstein Barr virus and human herpes virus type-8. Medicina 70:151–158PubMedGoogle Scholar
  23. Dave SS (2010) Host factors for risk and survival in lymphoma. In: ASH Education Program Book, pp. 255–258Google Scholar
  24. Davis RE, Brown KD, Siebenlist U, Staudt LM (2001) Constitutive nuclear factor κB activity is required for survival of activated B cell-like diffuse large B cell lymphoma cells. J Exp Med 194:1861–1874PubMedCentralPubMedCrossRefGoogle Scholar
  25. Davis RE et al (2010) Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma. Nature 463:88–92PubMedCentralPubMedCrossRefGoogle Scholar
  26. De Martel C et al (2012) Global burden of cancers attributable to infections in 2008: a review and synthetic analysis. Lancet Oncol 13:607–615PubMedCrossRefGoogle Scholar
  27. Ding BB et al (2008) Constitutively activated STAT3 promotes cell proliferation and survival in the activated B-cell subtype of diffuse large B-cell lymphomas. Blood 111:1515–1523PubMedCentralPubMedCrossRefGoogle Scholar
  28. Dojcinov SD et al (2011) Age-related EBV-associated lymphoproliferative disorders in the Western population: a spectrum of reactive lymphoid hyperplasia and lymphoma. Blood 117:4726–4735PubMedCentralPubMedCrossRefGoogle Scholar
  29. Eliopoulos AG et al (1997) Epstein-Barr virus-encoded LMP1 and CD40 mediate IL-6 production in epithelial cells via an NF-κB pathway involving TNF receptor-associated factors. Oncogene 14:2899–2916PubMedCrossRefGoogle Scholar
  30. Epstein MA, Achong BG, Barr YM (1964) Virus particles in cultured lymphoblasts from Burkitt’s lymphoma. The Lancet 283:702–703CrossRefGoogle Scholar
  31. Feng W-H, Hong G, Delecluse H-J, Kenney SC (2004) Lytic induction therapy for Epstein-Barr virus-positive B-cell lymphomas. J Virol 78:1893–1902PubMedCentralPubMedCrossRefGoogle Scholar
  32. Fisher SG, Fisher RI (2004) The epidemiology of non-Hodgkin’s lymphoma. Oncogene 23:6524–6534PubMedCrossRefGoogle Scholar
  33. Franke S et al (2002) Comparative genomic hybridization pattern distinguishes T-cell/histiocyte-rich B-cell lymphoma from nodular lymphocyte predominance Hodgkin’s lymphoma. Am J Pathol 161:1861–1867PubMedCentralPubMedCrossRefGoogle Scholar
  34. Gattinoni L, Powell DJ, Rosenberg SA, Restifo NP (2006) Adoptive immunotherapy for cancer: building on success. Nat Rev Immunol 6:383–393PubMedCentralPubMedCrossRefGoogle Scholar
  35. Ghosh SK, Perrine SP, Williams RM, Faller DV (2012) Histone deacetylase inhibitors are potent inducers of gene expression in latent EBV and sensitize lymphoma cells to nucleoside antiviral agents. Blood 119:1008–1017PubMedCentralPubMedCrossRefGoogle Scholar
  36. Gibson SE, Hsi ED (2009) Epstein-Barr virus-positive B-cell lymphoma of the elderly at a United States tertiary medical center: an uncommon aggressive lymphoma with a nongerminal center B-cell phenotype. Hum Pathol 40:653–661PubMedCrossRefGoogle Scholar
  37. Giles FJ, O’Brien SM, Keating MJ (1998) Chronic lymphocytic leukemia in (Richter’s) transformation. Semin Oncol 25:117–125PubMedGoogle Scholar
  38. Gloghini A, Dolcetti R, Carbone A (2013) Lymphomas occurring specifically in HIV-infected patients: from pathogenesis to pathology. Semin Cancer Biol 23:457–467PubMedCrossRefGoogle Scholar
  39. Gulley ML (2001) Molecular diagnosis of Epstein-Barr virus-related diseases. J Mol Diagn 3:1–10PubMedCentralPubMedCrossRefGoogle Scholar
  40. Hadrup SR et al (2006) Longitudinal studies of clonally expanded CD8 T cells reveal a repertoire shrinkage predicting mortality and an increased number of dysfunctional cytomegalovirus-specific T cells in the very elderly. J Immunol 176:2645–2653PubMedCrossRefGoogle Scholar
  41. Hans CP et al (2004) Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood 103:275–282PubMedCrossRefGoogle Scholar
  42. Heslop HE (2005) Biology and treatment of Epstein-Barr virus-associated non-Hodgkin lymphomas. In: Hematology/The Education Program of the American Society of Hematology. American Society of Hematology. Education Program, pp 260–266Google Scholar
  43. Hoeller S, Tzankov A, Pileri SA, Went P, Dirnhofer S (2010) Epstein-Barr virus–positive diffuse large B-cell lymphoma in elderly patients is rare in Western populations. Hum Pathol 41:352–357PubMedCrossRefGoogle Scholar
  44. Hofscheier A et al (2011) Geographic variation in the prevalence of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly: a comparative analysis of a Mexican and a German population. Mod Pathol 24:1046–1054PubMedCrossRefGoogle Scholar
  45. Hsi ED, Lorsbach RB, Fend F, Dogan A (2011) Plasmablastic lymphoma and related disorders. Am J Clin Pathol 136:183–194PubMedCrossRefGoogle Scholar
  46. Huen D, Henderson S, Croom-Carter D, Rowe M (1995) The Epstein-Barr virus latent membrane protein-1 (LMP1) mediates activation of NF-κB and cell surface phenotype via two effector regions in its carboxy-terminal cytoplasmic domain. Oncogene 10:549–560PubMedGoogle Scholar
  47. Igarashi M, Kawaguchi Y, Hirai K, Mizuno F (2003) Physical interaction of Epstein-Barr virus (EBV) nuclear antigen leader protein (EBNA-LP) with human oestrogen-related receptor 1 (hERR1): hERR1 interacts with a conserved domain of EBNA-LP that is critical for EBV-induced B-cell immortalization. J General Virol 84:319–327CrossRefGoogle Scholar
  48. Jemal A et al (2011) Global cancer statistics. CA Cancer J Clin 61:69–90PubMedCrossRefGoogle Scholar
  49. Jones JF, Straus SE (1987) Chronic epstein-barr virus infection. Annu Rev Med 38:195–209PubMedCrossRefGoogle Scholar
  50. Juvonen E et al (2003) High incidence of PTLD after non-T-cell-depleted allogeneic haematopoietic stem cell transplantation as a consequence of intensive immunosuppressive treatment. Bone Marrow Transplant 32:97–102PubMedCrossRefGoogle Scholar
  51. Kato M et al (2009) Frequent inactivation of A20 in B-cell lymphomas. Nature 459:712–716PubMedCrossRefGoogle Scholar
  52. Kato H et al (2014) Gene expression profiling of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly reveals alterations of characteristic oncogenetic pathways. Cancer Sci 105:537–544PubMedPubMedCentralCrossRefGoogle Scholar
  53. Kaye KM, Izumi KM, Kieff E (1993) Epstein-Barr virus latent membrane protein 1 is essential for B-lymphocyte growth transformation. Proc Natl Acad Sci 90:9150–9154PubMedCentralPubMedCrossRefGoogle Scholar
  54. Kroemer G (1997) The proto-oncogene Bcl-2 and its role in regulating apoptosis. Nat Med 3:614–620PubMedCrossRefGoogle Scholar
  55. Laichalk LL, Thorley-Lawson DA (2005) Terminal differentiation into plasma cells initiates the replicative cycle of Epstein-Barr virus in vivo. J Virol 79:1296–1307PubMedCentralPubMedCrossRefGoogle Scholar
  56. Lam LT et al (2008) Cooperative signaling through the signal transducer and activator of transcription 3 and nuclear factor-κB pathways in subtypes of diffuse large B-cell lymphoma. Blood 111:3701–3713PubMedCentralPubMedCrossRefGoogle Scholar
  57. Lenz G et al (2008a) Stromal gene signatures in large-B-cell lymphomas. N Engl J Med 359:2313–2323PubMedCrossRefGoogle Scholar
  58. Lenz G et al (2008b) Molecular subtypes of diffuse large B-cell lymphoma arise by distinct genetic pathways. Proc Natl Acad Sci USA 105:13520–13525PubMedCentralPubMedCrossRefGoogle Scholar
  59. Lenz G et al (2008c) Oncogenic CARD11 mutations in human diffuse large B cell lymphoma. Science 319:1676–1679PubMedCrossRefGoogle Scholar
  60. Lemon SM, Hutt LM, Shaw JE, Li, J-LH, Pagano JS (1977) Replication of EBV in epithelial cells during infectious mononucleosisGoogle Scholar
  61. Lim MS et al (2002) T-cell/histiocyte-rich large B-cell lymphoma: a heterogeneous entity with derivation from germinal center B cells. Am J Surg Pathol 26:1458–1466PubMedCrossRefGoogle Scholar
  62. Loong F et al (2010) Diffuse large B-cell lymphoma associated with chronic inflammation as an incidental finding and new clinical scenarios. Mod Pathol 23:493–501PubMedCrossRefGoogle Scholar
  63. Lopes LF et al (2013) Epstein-Barr virus (EBV) microRNAs: involvement in cancer pathogenesis and immunopathology. Int Rev Immunol 32:271–281PubMedCrossRefGoogle Scholar
  64. Martelli M et al (2013) Diffuse large B-cell lymphoma. Critical Rev Oncol Hematol 87:146–171CrossRefGoogle Scholar
  65. Menon MP, Pittaluga S, Jaffe ES (2012) The histological and biological spectrum of diffuse large B-cell lymphoma in the World Health Organization classification. Cancer J (Sudbury, Mass.) 18:411–420Google Scholar
  66. Miller RA (1996) The aging immune system: primer and prospectus. Science 273:70–74PubMedCrossRefGoogle Scholar
  67. Miranda RN, Khoury JD, Medeiros LJ (2013) Lymphoproliferative disorders associated with primary immune disorders. Atlas Lymph Node Pathol 383–397Google Scholar
  68. Montes-Moreno S et al (2012) EBV-positive diffuse large B-cell lymphoma of the elderly is an aggressive post-germinal center B-cell neoplasm characterized by prominent nuclear factor-kB activation. Mod Pathol 25:968–982PubMedCrossRefGoogle Scholar
  69. Morin RD et al (2013) Mutational and structural analysis of diffuse large B-cell lymphoma using whole-genome sequencing. Blood 122:1256–1265PubMedCentralPubMedCrossRefGoogle Scholar
  70. Muppidi JR et al (2014) Loss of signalling via Galpha13 in germinal centre B-cell-derived lymphoma. NatureGoogle Scholar
  71. Murase T et al (2007) Intravascular large B-cell lymphoma (IVLBCL): a clinicopathologic study of 96 cases with special reference to the immunophenotypic heterogeneity of CD5. Blood 109:478–485PubMedCrossRefGoogle Scholar
  72. Nakatsuka S-I et al (2002) Pyothorax-associated lymphoma: a review of 106 cases. J Clin Oncol 20:4255–4260PubMedCrossRefGoogle Scholar
  73. Narimatsu H et al (2007) Clinicopathological features of pyothorax-associated lymphoma; a retrospective survey involving 98 patients. Ann Oncol 18:122–128PubMedCrossRefGoogle Scholar
  74. Nguyen-Van D et al (2011) Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly expresses EBNA3A with conserved CD8 T-cell epitopes. Am J Blood Res 1:146–159PubMedCentralPubMedGoogle Scholar
  75. Niederman J, Evans A, Subrahmanyan L, McCollum R (1970) Prevalence, incidence and persistence of EB virus antibody in young adults. N Engl J Med 282:361–365PubMedCrossRefGoogle Scholar
  76. Nilsson K, Klein G, Henle W, Henle G (1971) The establishment of lymphoblastoid lines from adult and fetal human lymphoid tissue and its dependence on EBV. Int J cancer 8:443–450PubMedCrossRefGoogle Scholar
  77. Ok CY, Papathomas TG, Medeiros LJ, Young KH (2013) EBV-positive diffuse large B-cell lymphoma of the elderly. Blood 122:328–340PubMedCentralPubMedCrossRefGoogle Scholar
  78. Ok CY et al (2014) Prevalence and clinical implications of epstein-barr virus infection in de novo diffuse large B-cell lymphoma in Western countries. Clin Cancer Res Off J Am Assoc Cancer Res 20:2338–2349CrossRefGoogle Scholar
  79. Orthwein A, Di Noia JM (2012) Activation induced deaminase: how much and where? Semin Immunol 24:246–254PubMedCrossRefGoogle Scholar
  80. Ott G, Rosenwald A, Campo E (2013) Understanding MYC-driven aggressive B-cell lymphomas: pathogenesis and classification. Blood 122:3884–3891PubMedCrossRefGoogle Scholar
  81. Oyama T et al (2003) Senile EBV+ B-cell lymphoproliferative disorders: a clinicopathologic study of 22 patients. Am J Surg Pathol 27:16–26PubMedCrossRefGoogle Scholar
  82. Oyama T et al (2007) Age-related EBV-associated B-cell lymphoproliferative disorders constitute a distinct clinicopathologic group: a study of 96 patients. Clin Cancer Res Off J Am Assoc Cancer Res 13:5124–5132CrossRefGoogle Scholar
  83. Park S et al (2007) The impact of Epstein-Barr virus status on clinical outcome in diffuse large B-cell lymphoma. Blood 110:972–978PubMedCrossRefGoogle Scholar
  84. Pasqualucci L et al (2011) Analysis of the coding genome of diffuse large B-cell lymphoma. Nat Genet 43:830–837PubMedCentralPubMedCrossRefGoogle Scholar
  85. Piekarz RL et al (2011) Phase 2 trial of romidepsin in patients with peripheral T-cell lymphoma. Blood 117:5827–5834PubMedCentralPubMedCrossRefGoogle Scholar
  86. Pittaluga S, Jaffe ES (2010) T-cell/histiocyte-rich large B-cell lymphoma. Haematologica 95:352–356Google Scholar
  87. Ponzoni M et al (2007) Definition, diagnosis, and management of intravascular large B-cell lymphoma: proposals and perspectives from an international consensus meeting. J Clin Oncol 25:3168–3173PubMedCrossRefGoogle Scholar
  88. Rickinson AB (2014) Co-infections, inflammation and oncogenesis: future directions for EBV research. Semin Cancer Biol 26:99–115PubMedCrossRefGoogle Scholar
  89. Rickinson AB, Moss DJ (1997) Human cytotoxic T lymphocyte responses to Epstein-Barr virus infection. Annu Rev Immunol 15:405–431PubMedCrossRefGoogle Scholar
  90. Rosenwald A, Staudt LM (2003) Gene expression profiling of diffuse large B-cell lymphoma. Leuk Lymphoma 44(Suppl 3):S41–S47PubMedCrossRefGoogle Scholar
  91. Rosenwald A et al (2002) The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med 346:1937–1947PubMedCrossRefGoogle Scholar
  92. Roughan JE, Thorley-Lawson DA (2009) The intersection of Epstein-Barr virus with the germinal center. J Virol 83:3968–3976PubMedCentralPubMedCrossRefGoogle Scholar
  93. Schuetz JM et al (2012) BCL2 mutations in diffuse large B-cell lymphoma. Leukemia 26:1383–1390PubMedCrossRefGoogle Scholar
  94. Schulze-Luehrmann J, Ghosh S (2006) Antigen-receptor signaling to nuclear factor κB. Immunity 25:701–715PubMedCrossRefGoogle Scholar
  95. Sherritt MA et al (2003) Reconstitution of the latent T-lymphocyte response to Epstein-Barr virus is coincident with long-term recovery from posttransplant lymphoma after adoptive immunotherapy. Transplantation 75:1556–1560PubMedCrossRefGoogle Scholar
  96. Shimoyama Y et al (2008) Age-related Epstein-Barr virus-associated B-cell lymphoproliferative disorders: special references to lymphomas surrounding this newly recognized clinicopathologic disease. Cancer Sci 99:1085–1091PubMedCrossRefGoogle Scholar
  97. Smedby KE et al (2006) Autoimmune and chronic inflammatory disorders and risk of non-Hodgkin lymphoma by subtype. J Natl Cancer Inst 98:51–60PubMedCrossRefGoogle Scholar
  98. Staudt LM (2010) Oncogenic activation of NF-κB. Cold Spring Harb Perspect Biol 2:a000109PubMedCentralPubMedCrossRefGoogle Scholar
  99. Stein H, Lennert K, Feller AC (1984) Immunohistological analysis of human lymphoma: correlation of histological and immunological categories. Adv Cancer Res 42:67–147PubMedCrossRefGoogle Scholar
  100. Strnad J, Burke JR (2007) IκB kinase inhibitors for treating autoimmune and inflammatory disorders: potential and challenges. Trends Pharmacol Sci 28:142–148PubMedCrossRefGoogle Scholar
  101. Sun CC, Thorley-Lawson DA (2007) Plasma cell-specific transcription factor XBP-1 s binds to and transactivates the Epstein-Barr virus BZLF1 promoter. J Virol 81:13566–13577PubMedCentralPubMedCrossRefGoogle Scholar
  102. Swerdlow SH, Campo E, Harris NL et al (2008) WHO classification of tumours of haematopoetic and lymphoid tissues, 4th edn. IARC Press, LyonGoogle Scholar
  103. Tan S, Parker P (2003) Emerging and diverse roles of protein kinase C in immune cell signalling. Biochem J 376:545–552PubMedCentralPubMedCrossRefGoogle Scholar
  104. Taylor AL, Marcus R, Bradley JA (2005) Post-transplant lymphoproliferative disorders (PTLD) after solid organ transplantation. Crit Rev Oncol Hematol 56:155–167PubMedCrossRefGoogle Scholar
  105. Thorley-Lawson DA, Gross A (2004) Persistence of the Epstein-Barr virus and the origins of associated lymphomas. N Engl J Med 350:1328–1337PubMedCrossRefGoogle Scholar
  106. Tierney R, Steven N, Young L, Rickinson A (1994) Epstein-Barr virus latency in blood mononuclear cells: analysis of viral gene transcription during primary infection and in the carrier state. J Virol 68:7374–7385PubMedCentralPubMedGoogle Scholar
  107. Tsubata T, Wu J, Honjo T (1993) B-cell apoptosis induced by antigen receptor crosslinking is blocked by a T-cell signal through CD40Google Scholar
  108. Uchida J et al (1999) Mimicry of CD40 signals by Epstein-Barr virus LMP1 in B lymphocyte responses. Science 286:300–303PubMedCrossRefGoogle Scholar
  109. Uner A et al (2011) The presence of Epstein-Barr virus (EBV) in diffuse large B-cell lymphomas (DLBCLs) in Turkey: special emphasis on ‘EBV-positive DLBCL of the elderly’. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 119:309–316PubMedCrossRefGoogle Scholar
  110. Valera A et al (2010) IG/MYC rearrangements are the main cytogenetic alteration in plasmablastic lymphomas. Am J Surg Pathol 34:1686PubMedCentralPubMedGoogle Scholar
  111. Verma S et al (2005) Epstein-Barr virus- and human herpesvirus 8-associated primary cutaneous plasmablastic lymphoma in the setting of renal transplantation. J Cutan Pathol 32:35–39PubMedCrossRefGoogle Scholar
  112. Victora GD, Nussenzweig MC (2012) Germinal centers. Annu Rev Immunol 30:429–457PubMedCrossRefGoogle Scholar
  113. Wada N et al (2011) Epstein-barr virus in diffuse large B-Cell lymphoma in immunocompetent patients in Japan is as low as in Western Countries. J Med Virol 83:317–321PubMedCrossRefGoogle Scholar
  114. Yang Z-Z, Novak AJ, Stenson MJ, Witzig TE, Ansell SM (2006) Intratumoral CD4+ CD25+ regulatory T-cell-mediated suppression of infiltrating CD4+ T cells in B-cell non-Hodgkin lymphoma. Blood 107:3639–3646PubMedCentralPubMedCrossRefGoogle Scholar
  115. Younes A (2009) Novel treatment strategies for patients with relapsed classical Hodgkin lymphoma. ASH Education Program Book 2009:507–519Google Scholar
  116. Young LS, Murray PG (2003) Epstein-Barr virus and oncogenesis: from latent genes to tumours. Oncogene 22:5108–5121PubMedCrossRefGoogle Scholar
  117. Young LS, Rickinson AB (2004) Epstein-Barr virus: 40 years on. Nat Rev Cancer 4:757–768PubMedCrossRefGoogle Scholar
  118. Zhang J et al (2013) Genetic heterogeneity of diffuse large B-cell lymphoma. Proc Natl Acad Sci USA 110:1398–1403PubMedCentralPubMedCrossRefGoogle Scholar
  119. Ziepert M et al (2010) Standard International prognostic index remains a valid predictor of outcome for patients with aggressive CD20+ B-cell lymphoma in the rituximab era. J Clini Oncol Off J Am Soc Clin Oncol 28:2373–2380CrossRefGoogle Scholar
  120. Zou P, Kawada J, Pesnicak L, Cohen JI (2007) Bortezomib induces apoptosis of Epstein-Barr virus (EBV)-transformed B cells and prolongs survival of mice inoculated with EBV-transformed B cells. J Virol 81:10029–10036PubMedCentralPubMedCrossRefGoogle Scholar

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© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Department of Hematology/OncologyDuke UniversityDurhamUSA
  2. 2.Center for Genomic and Computational BiologyDuke UniversityDurhamUSA

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