Notch and NF-κB signaling pathways in the biology of classical Hodgkin lymphoma

Current Molecular Medicine

Volumn 11, Issue 3, 2011, Pages 236-245

  Schwarzer, R ^a   Jundt, F ^b  

^a CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^b MAX DELBRÜCK CENTER FOR MOLECULAR MEDICINE   (Germany)

Author keywords

B cell lymphoma; Hodgkin lymphoma; Hodgkin reed sternberg cells; NF B; Notch

Indexed keywords

ARSENIC; BIIB 021; BORTEZOMIB; CD30 ANTIGEN; CD40 ANTIGEN; HEAT SHOCK PROTEIN 90 INHIBITOR; HISTONE DEACETYLASE INHIBITOR; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; LATENT MEMBRANE PROTEIN 1; NOTCH RECEPTOR; NOTCH1 RECEPTOR; NOTCH2 RECEPTOR; PROTEASOME INHIBITOR; PROTEIN BCL 3; RECEPTOR ACTIVATOR OF NUCLEAR FACTOR KAPPA B; TRANSCRIPTION FACTOR GATA 2; TRANSCRIPTION FACTOR GATA 3; UNCLASSIFIED DRUG;

ANTIGEN EXPRESSION; ANTINEOPLASTIC ACTIVITY; ARTICLE; B LYMPHOCYTE; CANCER GROWTH; CELL COMMUNICATION; CELL PROLIFERATION; CELL SURVIVAL; CLASSICAL HODGKIN LYMPHOMA; DRUG POTENTIATION; EPSTEIN BARR VIRUS; GENE EXPRESSION REGULATION; GENE MUTATION; HUMAN; LYMPHOMA CELL; MOLECULAR PATHOLOGY; MOLECULARLY TARGETED THERAPY; NONHODGKIN LYMPHOMA; NONHUMAN; PROTEIN PROTEIN INTERACTION; REED STERNBERG CELL; SIGNAL TRANSDUCTION; TRANSCRIPTION INITIATION; TRANSCRIPTION REGULATION;

HUMAN HERPESVIRUS 4;

EID: 79953327512     PISSN: 15665240     EISSN: None     Source Type: Journal    
DOI: 10.2174/156652411795243423     Document Type: Article

References (139)

1. Staudt LM. The molecular and cellular origins of Hodgkin's disease. J Exp Med 2000; 191: 207-212.
2. Schmitz R, Stanelle J, Hansmann ML, Kuppers R. Pathogenesis of classical and lymphocyte-predominant Hodgkin lymphoma. Annu Rev Pathol 2009; 4: 151-174.
3. Kuppers R, Rajewsky K. The origin of Hodgkin and Reed/Sternberg cells in Hodgkin's disease. Annu Rev Immunol 1998; 16: 471-493.
4. Hodgkin T. On some Morbid Appearances of the Absorbent Glands and Spleen. Med Chir Trans 1832; 17: 68-114.
5. Reed D. On the pathological changes in Hodgkins disease with special reference to its relation to tuberculosis. John Hopkins Hosp Rep 1902; 10: 133-193.
6. Sternberg C. Über eine eigenartige unter dem Bilde der Pseudoleukämie verlaufende Tuberkulose des lymphatischen Apparates. Z Heilkunde 1898; 19: 21-90.
7. Kuppers R, Rajewsky K, Zhao M, et al. Hodgkin disease: Hodgkin and Reed-Sternberg cells picked from histological sections show clonal immunoglobulin gene rearrangements and appear to be derived from B cells at various stages of development. Proc Natl Acad Sci USA 1994; 91: 10962-10966.
8. Jaffe ES, Harris NL, Stein H, Isaacson PG. Classification of lymphoid neoplasms: the microscope as a tool for disease discovery. Blood 2008; 112: 4384-4399.
9. Marafioti T, Hummel M, Foss HD, et al. Hodgkin and reedsternberg cells represent an expansion of a single clone originating from a germinal center B-cell with functional immunoglobulin gene rearrangements but defective immunoglobulin transcription. Blood 2000; 95: 1443-1450.
10. Kanzler H, Kuppers R, Hansmann ML, Rajewsky K. Hodgkin and Reed-Sternberg cells in Hodgkin's disease represent the outgrowth of a dominant tumor clone derived from (crippled) germinal center B cells. J Exp Med 1996; 184: 1495-505.
11. Kuppers R, Zhao M, Hansmann ML, Rajewsky K. Tracing B cell development in human germinal centres by molecular analysis of single cells picked from histological sections. EMBO J 1993; 12: 4955-4967.
12. Brauninger A, Hansmann ML, Strickler JG, et al. Identification of common germinal-center B-cell precursors in two patients with both Hodgkin's disease and non-Hodgkin's lymphoma. N Engl J Med 1999; 340: 1239-1247.
13. Martin-Subero JI, Klapper W, Sotnikova A, et al. Chromosomal breakpoints affecting immunoglobulin loci are recurrent in Hodgkin and Reed-Sternberg cells of classical Hodgkin lymphoma. Cancer Res 2006; 66: 10332-10338.
14. Irsch J, Wolf J, Tesch H, Diehl V, Radbruch A, Staratschek-Jox A. Class switch recombination was specifically targeted to immunoglobulin (Ig)G4 or IgA in Hodgkin's diseasederived cell lines. Br J Haematol 2001; 113: 785-793.
15. Schwering I, Brauninger A, Klein U, et al. Loss of the Blineage-specific gene expression program in Hodgkin and Reed-Sternberg cells of Hodgkin lymphoma. Blood 2003; 101: 1505-1512.
16. Kuppers R. The biology of Hodgkin's lymphoma. Nat Rev Cancer 2009; 9: 15-27.
17. Kuppers R. Mechanisms of B-cell lymphoma pathogenesis. Nat Rev Cancer 2005; 5: 251-262.
18. Kuppers R, Klein U, Schwering I, et al. Identification of Hodgkin and Reed-Sternberg cell-specific genes by gene expression profiling. J Clin Invest 2003; 111: 529-537.
19. Bargou RC, Mapara MY, Zugck C, et al. Characterization of a novel Hodgkin cell line, HD-MyZ, with myelomonocytic features mimicking Hodgkin's disease in severe combined immunodeficient mice. J Exp Med 1993; 177: 1257-1268.
20. Jundt F, Kley K, Anagnostopoulos I, et al. Loss of PU.1 expression is associated with defective immunoglobulin transcription in Hodgkin and Reed-Sternberg cells of classical Hodgkin disease. Blood 2002; 99: 3060-3062.
21. Loddenkemper C, Anagnostopoulos I, Hummel M, et al. Differential Emu enhancer activity and expression of BOB.1/OBF.1, Oct2, PU.1, and immunoglobulin in reactive B-cell populations, B-cell non-Hodgkin lymphomas, and Hodgkin lymphomas. J Pathol 2004; 202: 60-69.
22. Stein H, Marafioti T, Foss HD, et al. Down-regulation of BOB.1/OBF.1 and Oct2 in classical Hodgkin disease but not in lymphocyte predominant Hodgkin disease correlates with immunoglobulin transcription. Blood 2001; 97: 496-501.
23. Hertel CB, Zhou XG, Hamilton-Dutoit SJ, Junker S. Loss of B cell identity correlates with loss of B cell-specific transcription factors in Hodgkin/Reed-Sternberg cells of classical Hodgkin lymphoma. Oncogene 2002; 21: 4908-4920.
24. Theil J, Laumen H, Marafioti T, et al. Defective octamerdependent transcription is responsible for silenced immunoglobulin transcription in Reed-Sternberg cells. Blood 2001; 97: 3191-3196.
25. Re D, Muschen M, Ahmadi T, et al. Oct-2 and Bob-1 deficiency in Hodgkin and Reed Sternberg cells. Cancer Res 2001; 61: 2080-2084.
26. Chang JF, Phillips K, Lundback T, Gstaiger M, Ladbury JE, Luisi B. Oct-1 POU and octamer DNA co-operate to recognise the Bob-1 transcription co-activator via induced folding. J Mol Biol 1999; 288: 941-952.
27. Laumen H, Nielsen PJ, Wirth T. The BOB.1 / OBF.1 coactivator is essential for octamer-dependent transcription in B cells. Eur J Immunol 2000; 30: 458-469.
28. Shah PC, Bertolino E, Singh H. Using altered specificity Oct- 1 and Oct-2 mutants to analyze the regulation of immunoglobulin gene transcription. EMBO J 1997; 16: 7105-7117.
29. Torlakovic E, Tierens A, Dang HD, Delabie J. The transcription factor PU.1, necessary for B-cell development is expressed in lymphocyte predominance, but not classical Hodgkin's disease. Am J Pathol 2001; 159: 1807-1814.
30. Jox A, Zander T, Kuppers R, et al. Somatic mutations within the untranslated regions of rearranged Ig genes in a case of classical Hodgkin's disease as a potential cause for the absence of Ig in the lymphoma cells. Blood 1999; 93: 3964-3972
31. Ushmorov A, Ritz O, Hummel M, et al. Epigenetic silencing of the immunoglobulin heavy-chain gene in classical Hodgkin lymphoma-derived cell lines contributes to the loss of immunoglobulin expression. Blood 2004; 104: 3326-3334.
32. Doerr JR, Malone CS, Fike FM, et al. Patterned CpG methylation of silenced B cell gene promoters in classical Hodgkin lymphoma-derived and primary effusion lymphoma cell lines. J Mol Biol 2005; 350: 631-640.
33. Ushmorov A, Leithauser F, Sakk O, et al. Epigenetic processes play a major role in B-cell-specific gene silencing in classical Hodgkin lymphoma. Blood 2006; 107: 2493-2500.
34. Ehlers A, Oker E, Bentink S, Lenze D, Stein H, Hummel M. Histone acetylation and DNA demethylation of B cells result in a Hodgkin-like phenotype. Leukemia 2008; 22: 835-841.
35. Kopan R, Ilagan MX. The canonical Notch signaling pathway: unfolding the activation mechanism. Cell 2009; 137: 216-233.
36. Jundt F, Anagnostopoulos I, Forster R, Mathas S, Stein H, Dorken B. Activated Notch1 signaling promotes tumor cell proliferation and survival in Hodgkin and anaplastic large cell lymphoma. Blood 2002; 99: 3398-3403.
37. Schneider EM, Torlakovic E, Stuhler A, Diehl V, Tesch H, Giebel B. The early transcription factor GATA-2 is expressed in classical Hodgkin's lymphoma. J Pathol 2004; 204: 538-545.
38. Atayar C, Poppema S, Blokzijl T, Harms G, Boot M, van den Berg A. Expression of the T-cell transcription factors, GATA-3 and T-bet, in the neoplastic cells of Hodgkin lymphomas. Am J Pathol 2005; 166: 127-134.
39. Stanelle J, Doring C, Hansmann ML, Kuppers R. Mechanisms of aberrant GATA3 expression in classical Hodgkin lymphoma and its consequences for the cytokine profile of Hodgkin and Reed/Sternberg cells. Blood 2010; 116: 4202-4011.
40. Mathas S, Janz M, Hummel F, et al. Intrinsic inhibition of transcription factor E2A by HLH proteins ABF-1 and Id2 mediates reprogramming of neoplastic B cells in Hodgkin lymphoma. Nat Immunol 2006; 7: 207-215.
41. Renne C, Martin-Subero JI, Eickernjager M, et al. Aberrant expression of ID2, a suppressor of B-cell-specific gene expression, in Hodgkin's lymphoma. Am J Pathol 2006; 169: 655-664.
42. Jundt F, Acikgoz O, Kwon SH, et al. Aberrant expression of Notch1 interferes with the B-lymphoid phenotype of neoplastic B cells in classical Hodgkin lymphoma. Leukemia 2008; 22: 1587-1594.
43. Anderson LJ, Longnecker R. Epstein-Barr virus latent membrane protein 2A exploits Notch1 to alter B-cell identity in vivo. Blood 2009; 113: 108-116.
44. Portis T, Dyck P, Longnecker R. Epstein-Barr Virus (EBV) LMP2A induces alterations in gene transcription similar to those observed in Reed-Sternberg cells of Hodgkin lymphoma. Blood 2003; 102: 4166-4178.
45. Portis T, Longnecker R. Epstein-Barr virus LMP2A interferes with global transcription factor regulation when expressed during B-lymphocyte development. J Virol 2003; 77: 105-114.
46. Deacon EM, Pallesen G, Niedobitek G, et al. Epstein-Barr virus and Hodgkin's disease: transcriptional analysis of virus latency in the malignant cells. J Exp Med 1993; 177: 339-349.
47. Caldwell RG, Wilson JB, Anderson SJ, Longnecker R. Epstein-Barr virus LMP2A drives B cell development and survival in the absence of normal B cell receptor signals. Immunity 1998; 9: 405-411.
48. Morimura T, Miyatani S, Kitamura D, Goitsuka R. Notch signaling suppresses IgH gene expression in chicken B cells: implication in spatially restricted expression of Serrate2/Notch1 in the bursa of Fabricius. J Immunol 2001; 166: 3277-3283.
49. Strobl LJ, Hofelmayr H, Marschall G, Brielmeier M, Bornkamm GW, Zimber-Strobl U. Activated Notch1 modulates gene expression in B cells similarly to Epstein-Barr viral nuclear antigen 2. J Virol 2000; 74: 1727-1735.
50. Kohlhof H, Hampel F, Hoffmann R, et al. Notch1, Notch2, and Epstein-Barr virus-encoded nuclear antigen 2 signaling differentially affects proliferation and survival of Epstein-Barr virus-infected B cells. Blood 2009; 113: 5506-5515.
51. Kochert K, Ullrich K, Kreher S, et al. High-level expression of Mastermind-like 2 contributes to aberrant activation of the NOTCH signaling pathway in human lymphomas. Oncogene Nov 29 [Epub ahead of print] 2010.
52. Greiner A, Tobollik S, Buettner M, et al. Differential expression of activation-induced cytidine deaminase (AID) in nodular lymphocyte-predominant and classical Hodgkin lymphoma. J Pathol 2005; 205: 541-547.
53. Jundt F, Schwarzer R, Dorken B. Notch signaling in leukemias and lymphomas. Curr Mol Med 2008; 8: 51-59.
54. Houde C, Li Y, Song L, et al. Overexpression of the NOTCH ligand JAG2 in malignant plasma cells from multiple myeloma patients and cell lines. Blood 2004; 104: 3697-3704.
55. Jundt F, Probsting KS, Anagnostopoulos I, et al. Jagged1-induced Notch signaling drives proliferation of multiple myeloma cells. Blood 2004; 103: 3511-3515.
56. Nefedova Y, Cheng P, Alsina M, Dalton WS, Gabrilovich DI. Involvement of Notch-1 signaling in bone marrow stromamediated de novo drug resistance of myeloma and other malignant lymphoid cell lines. Blood 2004; 103: 3503-3510.
57. Nefedova Y, Sullivan DM, Bolick SC, Dalton WS, Gabrilovich DI. Inhibition of Notch signaling induces apoptosis of myeloma cells and enhances sensitivity to chemotherapy. Blood 2008; 111: 2220-2229.
58. Rosati E, Sabatini R, Rampino G, et al. Constitutively activated Notch signaling is involved in survival and apoptosis resistance of B-CLL cells. Blood 2009; 113: 856-865.
59. Hubmann R, Schwarzmeier JD, Shehata M, et al. Notch2 is involved in the overexpression of CD23 in B-cell chronic lymphocytic leukemia. Blood 2002; 99: 3742-3747.
60. Bargou RC, Leng C, Krappmann D, et al. High-level nuclear NF-kappa B and Oct-2 is a common feature of cultured Hodgkin/Reed-Sternberg cells. Blood 1996; 87: 4340-4347.
61. Bargou RC, Emmerich F, Krappmann D, et al. Constitutive nuclear factor-kappaB-RelA activation is required for proliferation and survival of Hodgkin's disease tumor cells. J Clin Invest 1997; 100: 2961-2969.
62. Krappmann D, Emmerich F, Kordes U, Scharschmidt E, Dorken B, Scheidereit C. Molecular mechanisms of constitutive NF-kappaB/Rel activation in Hodgkin/Reed-Sternberg cells. Oncogene 1999; 18: 943-953.
63. Emmerich F, Meiser M, Hummel M, et al. 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 1999; 94: 3129-3134.
64. Cabannes E, Khan G, Aillet F, Jarrett RF, Hay RT. Mutations in the IkBa gene in Hodgkin's disease suggest a tumour suppressor role for IkappaBalpha. Oncogene 1999; 18:3063-3070.
65. Jungnickel B, Staratschek-Jox A, Brauninger A, et al. Clonal deleterious mutations in the IkappaBalpha gene in the malignant cells in Hodgkin's lymphoma. J Exp Med 2000; 191: 395-402.
66. Emmerich F, Theurich S, Hummel M, et al. Inactivating I kappa B epsilon mutations in Hodgkin/Reed-Sternberg cells. J Pathol 2003; 201: 413-420.
67. Martin-Subero JI, Gesk S, Harder L, et al. Recurrent involvement of the REL and BCL11A loci in classical Hodgkin lymphoma. Blood 2002; 99: 1474-1477.
68. Barth TF, Martin-Subero JI, Joos S, et al. Gains of 2p involving the REL locus correlate with nuclear c-Rel protein accumulation in neoplastic cells of classical Hodgkin lymphoma. Blood 2003; 101: 3681-3686.
69. Joos S, Menz CK, Wrobel G, et al. Classical Hodgkin lymphoma is characterized by recurrent copy number gains of the short arm of chromosome 2. Blood 2002; 99: 1381-1387.
70. Mathas S, Johrens K, Joos S, et al. Elevated NF-kappaB p50 complex formation and Bcl-3 expression in classical Hodgkin, anaplastic large-cell, and other peripheral T-cell lymphomas. Blood 2005; 106: 4287-4293.
71. Nishikori M, Maesako Y, Ueda C, Kurata M, Uchiyama T, Ohno H. High-level expression of BCL3 differentiates t(2;5)(p23;q35)-positive anaplastic large cell lymphoma from Hodgkin disease. Blood 2003; 101: 2789-2796.
72. Schmitz R, Hansmann ML, Bohle V, et al. TNFAIP3 (A20) is a tumor suppressor gene in Hodgkin lymphoma and primary mediastinal B cell lymphoma. J Exp Med 2009; 206: 981-989.
73. Annunziata CM, Safiran YJ, Irving SG, Kasid UN, Cossman J. Hodgkin disease: pharmacologic intervention of the CD40-NF kappa B pathway by a protease inhibitor. Blood 2000; 96:2841-2848.
74. Carbone A, Gloghini A, Gruss HJ, Pinto A. CD40 antigen expression on Reed-Sternberg cells. A reliable diagnostic tool for Hodgkin's disease. Am J Pathol 1995; 146: 780-781.
75. 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 2001; 97: 2798-2807.
76. Messineo C, Jamerson MH, Hunter E, et al. Gene expression by single Reed-Sternberg cells: pathways of apoptosis and activation. Blood 1998; 91: 2443-2451.
77. Izban KF, Ergin M, Martinez RL, Alkan S. Expression of the tumor necrosis factor receptor-associated factors (TRAFs) 1 and 2 is a characteristic feature of Hodgkin and Reed-Sternberg cells. Mod Pathol 2000; 13: 1324-1331.
78. Durkop H, Foss HD, Demel G, Klotzbach H, Hahn C, Stein H. Tumor necrosis factor receptor-associated factor 1 is overexpressed in Reed-Sternberg cells of Hodgkin's disease and Epstein-Barr virus-transformed lymphoid cells. Blood 1999; 93: 617-623.
79. Guo F, Sun A, Wang W, et al. TRAF1 is involved in the classical NF-kappaB activation and CD30-induced alternative activity in Hodgkin's lymphoma cells. Mol Immunol 2009; 46: 2441-2448.
80. Lavorgna A, De Filippi R, Formisano S, Leonardi A. TNF receptor-associated factor 1 is a positive regulator of the NFkappaB alternative pathway. Mol Immunol 2009; 46: 3278-3282.
81. Horie R, Watanabe T, Ito K, et al. Cytoplasmic aggregation of TRAF2 and TRAF5 proteins in the Hodgkin-Reed-Sternberg cells. Am J Pathol 2002; 160: 1647-1654.
82. Horie R, Aizawa S, Nagai M, et al. A novel domain in the CD30 cytoplasmic tail mediates NFkappaB activation. Int Immunol 1998; 10: 203-210.
83. Pinto A, Aldinucci D, Gloghini A, et al. Human eosinophils express functional CD30 ligand and stimulate proliferation of a Hodgkin's disease cell line. Blood 1996; 88: 3299-3305.
84. Gruss HJ, Pinto A, Gloghini A, et al. CD30 ligand expression in nonmalignant and Hodgkin's disease-involved lymphoid tissues. Am J Pathol 1996; 149: 469-481.
85. Horie R, Watanabe T, Morishita Y, et al. Ligand-independent signaling by overexpressed CD30 drives NF-kappaB activation in Hodgkin-Reed-Sternberg cells. Oncogene 2002;21: 2493-2503.
86. 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 2005; 24: 3976-3986.
87. Hirsch B, Hummel M, Bentink S, et al. CD30-induced signaling is absent in Hodgkin's cells but present in anaplastic large cell lymphoma cells. Am J Pathol 2008; 172:510-520.
88. Wahl AF, Klussman K, Thompson JD, et al. The anti-CD30 monoclonal antibody SGN-30 promotes growth arrest and DNA fragmentation in vitro and affects antitumor activity in models of Hodgkin's disease. Cancer Res 2002; 62: 3736-3742.
89. Chiu A, Xu W, He B, et al. Hodgkin lymphoma cells express TACI and BCMA receptors and generate survival and proliferation signals in response to BAFF and APRIL. Blood 2007; 109: 729-739.
90. Schwaller J, Went P, Matthes T, et al. Paracrine promotion of tumor development by the TNF ligand APRIL in Hodgkin's Disease. Leukemia 2007; 21: 1324-1327.
91. Fiumara P, Snell V, Li Y, et al. Functional expression of receptor activator of nuclear factor kappaB in Hodgkin disease cell lines. Blood 2001; 98: 2784-2790.
92. Saitoh Y, Yamamoto N, Dewan MZ, et al. Overexpressed NF-kappaB-inducing kinase contributes to the tumorigenesis of adult T-cell leukemia and Hodgkin Reed-Sternberg cells. Blood 2008; 111: 5118-5129.
93. Kutok JL, Wang F. Spectrum of Epstein-Barr virusassociated diseases. Annu Rev Pathol 2006; 1: 375-404.
94. Kanavaros P, Jiwa M, van der Valk P, Walboomers J, Horstman A, Meijer CJ. Expression of Epstein-Barr virus latent gene products and related cellular activation and adhesion molecules in Hodgkin's disease and non-Hodgkin's lymphomas arising in patients without overt pre-existing immunodeficiency. Hum Pathol 1993; 24: 725-729.
95. Armstrong AA, Gallagher A, Krajewski AS, et al. The expression of the EBV latent membrane protein (LMP-1) is independent of CD23 and bcl-2 in Reed-Sternberg cells in Hodgkin's disease. Histopathology 1992; 21: 72-73.
96. Sandvej KB, Hamilton-Dutoit SJ, Pallesen G. Influence of Epstein-Barr virus encoded latent membrane protein 1 on the expression of CD23 antigen, ICAM-1 and LFA-3 in Hodgkin and Reed-Sternberg cells. A morphometric analysis. Leuk Lymphoma 1993; 9: 95-101.
97. Mancao C, Hammerschmidt W. Epstein-Barr virus latent membrane protein 2A is a B-cell receptor mimic and essential for B-cell survival. Blood 2007; 110: 3715-3721.
98. Bechtel D, Kurth J, Unkel C, Kuppers 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 2005; 106: 4345-4350.
99. Altmann M, Pich D, Ruiss R, Wang J, Sugden B, Hammerschmidt W. Transcriptional activation by EBV nuclear antigen 1 is essential for the expression of EBV's transforming genes. Proc Natl Acad Sci USA 2006; 103:14188-14193.
100. Dolcetti R, Quaia M, Gloghini A, et al. Biologically relevant phenotypic changes and enhanced growth properties induced in B lymphocytes by an EBV strain derived from a histologically aggressive Hodgkin's disease. Int J Cancer 1999; 80: 240-249.
101. Wilson JB, Bell JL, Levine AJ. Expression of Epstein-Barr virus nuclear antigen-1 induces B cell neoplasia in transgenic mice. EMBO J 1996; 15: 3117-3126.
102. Huen DS, Henderson SA, 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 1995; 10: 549-560.
103. Cahir McFarland ED, Izumi KM, Mosialos G. Epstein-barr virus transformation: involvement of latent membrane protein 1-mediated activation of NF-kappaB. Oncogene 1999; 18:6959-6964.
104. Kaye KM, Devergne O, Harada JN, et al. Tumor necrosis factor receptor associated factor 2 is a mediator of NF-kappa B activation by latent infection membrane protein 1, the Epstein-Barr virus transforming protein. Proc Natl Acad Sci USA 1996; 93: 11085-11090.
105. Kulwichit W, Edwards RH, Davenport EM, Baskar JF, Godfrey V, Raab-Traub N. Expression of the Epstein-Barr virus latent membrane protein 1 induces B cell lymphoma in transgenic mice. Proc Natl Acad Sci USA 1998; 95: 11963-11968.
106. Stewart S, Dawson CW, Takada K, et al. Epstein-Barr virusencoded LMP2A regulates viral and cellular gene expression by modulation of the NF-kappaB transcription factor pathway. Proc Natl Acad Sci USA 2004; 101: 15730-15735.
107. Guasparri I, Bubman D, Cesarman E. EBV LMP2A affects LMP1-mediated NF-kappaB signaling and survival of lymphoma cells by regulating TRAF2 expression. Blood 2008; 111: 3813-3820.
108. Osipo C, Golde TE, Osborne BA, Miele LA. Off the beaten pathway: the complex cross talk between Notch and FkappaB. Lab Invest 2008; 88: 11-17.
109. Cheng P, Zlobin A, Volgina V, et al. Notch-1 regulates NFkappaB activity in hemopoietic progenitor cells. J Immunol 2001; 167: 4458-4467.
110. Oswald F, Liptay S, Adler G, Schmid RM. NF-kappaB2 is a putative target gene of activated Notch-1 via RBP-Jkappa. Mol Cell Biol 1998; 18: 2077-2088.
111. Bash J, Zong WX, Banga S, et al. Rel/NF-kappaB can trigger the Notch signaling pathway by inducing the expression of Jagged1, a ligand for Notch receptors. EMBO J 1999; 18: 2803-2811.
112. Guan E, Wang J, Laborda J, Norcross M, Baeuerle PA, Hoffman T. T cell leukemia-associated human Notch/translocation-associated Notch homologue has I kappa B-like activity and physically interacts with nuclear factor-kappa B proteins in T cells. J Exp Med 1996; 183: 2025-2032.
113. Wang J, Shelly L, Miele L, Boykins R, Norcross MA, Guan E. Human Notch-1 inhibits NF-kappa B activity in the nucleus through a direct interaction involving a novel domain. J Immunol 2001; 167: 289-295.
114. Bellavia D, Campese AF, Checquolo S, et al. Combined expression of pTalpha and Notch3 in T cell leukemia identifies the requirement of preTCR for leukemogenesis. Proc Natl Acad Sci USA 2002; 99: 3788-3793.
115. Vilimas T, Mascarenhas J, Palomero T, et al. Targeting the NF-kappaB signaling pathway in Notch1-induced T-cell leukemia. Nat Med 2007; 13: 70-77.
116. Jundt F, Raetzel N, Muller C, et al. A rapamycin derivative (everolimus) controls proliferation through down-regulation of truncated CCAAT enhancer binding protein {beta} and NF-{kappa}B activity in Hodgkin and anaplastic large cell lymphomas. Blood 2005; 106: 1801-1807.
117. Mathas S, Lietz A, Janz M, et al. Inhibition of NF-kappaB essentially contributes to arsenic-induced apoptosis. Blood 2003; 102: 1028-1034.
118. Blum KA, Johnson JL, Niedzwiecki D, Canellos GP, Cheson BD, Bartlett NL. Single agent bortezomib in the treatment of relapsed and refractory Hodgkin lymphoma: cancer and leukemia Group B protocol 50206. Leuk Lymph 2007; 48: 1313-1319.
119. Zhao X, Qiu W, Kung J, et al. Bortezomib induces caspasedependent apoptosis in Hodgkin lymphoma cell lines and is associated with reduced c-FLIP expression: a gene expression profiling study with implications for potential combination therapies. Leuk Res 2008; 32: 275-285.
120. Kashkar H, Deggerich A, Seeger JM, et al. NF-kappaBindependent down-regulation of XIAP by bortezomib sensitizes HL B cells against cytotoxic drugs. Blood 2007;109: 3982-3988.
121. Zheng B, Georgakis GV, Li Y, et al. Induction of cell cycle arrest and apoptosis by the proteasome inhibitor PS-341 in Hodgkin disease cell lines is independent of inhibitor of nuclear factor-kappaB mutations or activation of the CD30, CD40, and RANK receptors. Clin Cancer Res 2004; 10:3207-3215.
122. Bhalla S, Balasubramanian S, David K, et al. PCI-24781 induces caspase and reactive oxygen species-dependent apoptosis through NF-kappaB mechanisms and is synergistic with bortezomib in lymphoma cells. Clin Cancer Res 2009; 15: 3354-3365.
123. Buglio D, Mamidipudi V, Khaskhely NM, et al. The class-I HDAC inhibitor MGCD0103 induces apoptosis in Hodgkin lymphoma cell lines and synergizes with proteasome inhibitors by an HDAC6-independent mechanism. Br J Haematol 2010; 151: 387-396.
124. Boll B, Eltaib F, Reiners KS, et al. Heat shock protein 90 inhibitor BIIB021 (CNF2024) depletes NF-kappaB and sensitizes Hodgkin's lymphoma cells for natural killer cellmediated cytotoxicity. Clin Cancer Res 2009; 15: 5108-5116.
125. Nakashima M, Ishii Y, Watanabe M, et al. The side population, as a precursor of Hodgkin and Reed-Sternberg cells and a target for nuclear factor-kappaB inhibitors in Hodgkin's lymphoma. Cancer Sci 2010; 101: 2490-2496.
126. Kuppers R. Side population cells in Hodgkin lymphoma. Leuk Lymph 2010; 51: 741-742.
127. Ward RJ, Dirks PB. Cancer stem cells: at the headwaters of tumor development. Annu Rev Pathol 2007; 2: 175-189.
128. Yang ZJ, Wechsler-Reya RJ. Hitem where they live: targeting the cancer stem cell niche. Cancer Cell 2007; 11: 3-5.
129. Shafer JA, Cruz CR, Leen AM, et al. Antigen-specific cytotoxic T lymphocytes can target chemoresistant sidepopulation tumor cells in Hodgkin lymphoma. Leuk Lymph 2010; 51: 870-880.
130. Martinez-Climent JA, Fontan L, Gascoyne RD, Siebert R, Prosper F. Lymphoma stem cells: enough evidence to support their existence? Haematologica 2010; 95: 293-302.
131. Newcom SR, Kadin ME, Phillips C. L-428 Reed-Sternberg cells and mononuclear Hodgkin's cells arise from a single cloned mononuclear cell. Int J Cell Cloning 1988; 6: 417-431.
132. Jansen MP, Hopman AH, Bot FJ, et al. Morphologically normal, CD30-negative B-lymphocytes with chromosome aberrations in classical Hodgkin's disease: the progenitor cell of the malignant clone? J Pathol 1999; 189: 527-532.
133. Jansen MP, Hopman AH, Haesevoets AM, et al. Chromosomal abnormalities in Hodgkin's disease are not restricted to Hodgkin/Reed-Sternberg cells. J Pathol 1998; 185: 145-152.
134. Spieker T, Kurth J, Kuppers R, Rajewsky K, Brauninger A, Hansmann ML. Molecular single-cell analysis of the clonal relationship of small Epstein-Barr virus-infected cells and Epstein-Barr virus-harboring Hodgkin and Reed/Sternberg cells in Hodgkin disease. Blood 2000; 96: 3133-3138.
135. Vockerodt M, Soares M, Kanzler H, et al. Detection of clonal Hodgkin and Reed-Sternberg cells with identical somatically mutated and rearranged VH genes in different biopsies in relapsed Hodgkin's disease. Blood 1998; 92: 2899-2907.
136. Jones RJ, Gocke CD, Kasamon YL, et al. Circulating clonotypic B cells in classic Hodgkin lymphoma. Blood 2009; 113: 5920-5926.
137. Kuppers R. Clonotypic B cells in classic Hodgkin lymphoma. Blood 2009; 114: 3970-3971; author reply 1-2.
138. Pannuti A, Foreman K, Rizzo P, et al. Targeting Notch to target cancer stem cells. Clin Cancer Res 2010; 16: 3141-3152.
139. Bolos V, Blanco M, Medina V, Aparicio G, Diaz-Prado S, Grande E. Notch signalling in cancer stem cells. Clin Transl Oncol 2009; 11: 11-19.