• 1
    Bukh J, Miller RH, Purcell RH. Genetic heterogeneity of hepatitis C virus: quasispecies and genotypes. Semin Liver Dis 1995; 15: 4163.
  • 2
    Cerny A, Chisari FV. Pathogenesis of chronic hepatitis C: immunological features of hepatic injury and viral persistence. HEPATOLOGY 1999; 30: 595601.
  • 3
    Saito I, Miyamura T, Ohbayashi A, Harada H, Katayama T, Kikuchi S, et al. Hepatitis C virus infection is associated with the development of hepatocellular carcinoma. Proc Natl Acad Sci U S A 1990; 87: 65476549.
  • 4
    Dammacco F, Sansonno D, Piccoli C, Racanelli V, D′Amore FP, Lauletta G. The lymphoid system in hepatitis C virus infection: autoimmunity, mixed cryoglobulinemia, and overt B-cell malignancy. Semin Liver Dis 2000; 20: 143157.
  • 5
    Matsuo K, Kusano A, Sugumar A, Nakamura S, Tajima K, Mueller NE. Effect of hepatitis C virus infection on the risk of non-Hodgkin's lymphoma: a meta-analysis of epidemiological studies. Cancer Sci 2004; 95: 745752.
  • 6
    Matsuda F, Ishii K, Bourvagnet P, Kuma K, Hayashida H, Miyata T, et al. The complete nucleotide sequence of the human immunoglobulin heavy chain variable region locus. J Exp Med 1998; 188: 21512162.
  • 7
    Wilson PC, Wilson K, Liu YJ, Banchereau J, Pascual V, Capra JD. Receptor revision of immunoglobulin heavy chain variable region genes in normal human B lymphocytes. J Exp Med 2000; 191: 18811894.
  • 8
    Lai MM, Ware CF. Hepatitis C virus core protein: possible roles in viral pathogenesis. Curr Top Microbiol Immunol 2000; 242: 117134.
  • 9
    Kwong AD, Kim JL, Lin C. Structure and function of hepatitis C virus NS3 helicase. Curr Top Microbiol Immunol 2000; 242: 171196.
  • 10
    Chung YL, Sheu ML, Yen SH. Hepatitis C virus NS5A as a potential viral Bcl-2 homologue interacts with Bax and inhibits apoptosis in hepatocellular carcinoma. Int J Cancer 2003; 107: 6573.
  • 11
    Zignego AL, Giannelli F, Marrocchi ME, Mazzocca A, Ferri C, Giannini C, et al. T(14;18) translocation in chronic hepatitis C virus infection. HEPATOLOGY 2000; 31: 474479.
  • 12
    Weiss LM, Warnke RA, Sklar J, Cleary ML. Molecular analysis of the t(14;18) chromosomal translocation in malignant lymphomas. N Engl J Med 1987; 317: 11851189.
  • 13
    Kitay-Cohen Y, Amiel A, Hilzenrat N, Buskila D, Ashur Y, Fejgin M, et al. Bcl-2 rearrangement in patients with chronic hepatitis C associated with essential mixed cryoglobulinemia type II. Blood 2000; 96: 29102912.
  • 14
    Zuckerman E, Zuckerman T, Sahar D, Streichman S, Attias D, Sabo E, et al. bcl-2 and immunoglobulin gene rearrangement in patients with hepatitis C virus infection. Br J Haematol 2001; 112: 364369.
  • 15
    Zuckerman E, Zuckerman T, Sahar D, Streichman S, Attias D, Sabo E, et al. The effect of antiviral therapy on t(14;18) translocation and immunoglobulin gene rearrangement in patients with chronic hepatitis C virus infection. Blood 2001; 97: 15551559.
  • 16
    Zignego AL, Ferri C, Giannelli F, Giannini C, Caini P, Monti M, et al. Prevalence of bcl-2 rearrangement in patients with hepatitis C virus-related mixed cryoglobulinemia with or without B-cell lymphomas. Ann Intern Med 2002; 137: 571580.
  • 17
    Sansonno D, De Vita S, Iacobelli AR, Cornacchiulo V, Boiocchi M, Dammacco F. Clonal analysis of intrahepatic B cells from HCV-infected patients with and without mixed cryoglobulinemia. J Immunol 1998; 160: 35943601.
  • 18
    Racanelli V, Sansonno D, Piccoli C, D′Amore FP, Tucci FA, Dammacco F. Molecular characterization of B cell clonal expansions in the liver of chronically hepatitis C virus-infected patients. J Immunol 2001; 167: 2129.
  • 19
    Sansonno D, Lauletta G, De Re V, Tucci FA, Gatti P, Racanelli V, et al. Intrahepatic B cell clonal expansions and extrahepatic manifestations of chronic HCV infection. Eur J Immunol 2004; 34: 126136.
  • 20
    De Re V, De Vita S, Marzotto A, Rupolo M, Gloghini A, Pivetta B, et al. Sequence analysis of the immunoglobulin antigen receptor of hepatitis C virus-associated non-Hodgkin lymphomas suggests that the malignant cells are derived from the rheumatoid factor-producing cells that occur mainly in type II cryoglobulinemia. Blood 2000; 96: 35783584.
  • 21
    Durandy A. Activation-induced cytidine deaminase: a dual role in class-switch recombination and somatic hypermutation. Eur J Immunol 2003; 33: 20692073.
  • 22
    Pasqualucci L, Neumeister P, Goossens T, Nanjangud G, Chaganti RS, Kuppers R, et al. Hypermutation of multiple proto-oncogenes in B-cell diffuse large-cell lymphomas. Nature 2001; 412: 341346.
  • 23
    Ishak K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F, et al. Histological grading and staging of chronic hepatitis. J Hepatol 1995; 22: 696699.
  • 24
    Dammacco F, Sansonno D, Piccoli C, Tucci FA, Racanelli V. The cryoglobulins: an overview. Eur J Clin Invest 2001; 31: 628638.
  • 25
    Zhang L, Cui X, Schmitt K, Hubert R, Navidi W, Arnheim N. Whole genome amplification from a single cell: implications for genetic analysis. Proc Natl Acad Sci U S A 1992; 89: 58475851.
  • 26
    van Dongen JJ, Langerak AW, Bruggemann M, Evans PA, Hummel M, Lavender FL, et al. Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98–3936. Leukemia 2003; 17: 22572317.
  • 27
    Willis TG, Jadayel DM, Coignet LJ, Abdul-Rauf M, Treleaven JG, Catovsky D, et al. Rapid molecular cloning of rearrangements of the IGHJ locus using long-distance inverse polymerase chain reaction. Blood 1997; 90: 24562464.
  • 28
    Summers KE, Goff LK, Wilson AG, Gupta RK, Lister TA, Fitzgibbon J. Frequency of the Bcl-2/IgH rearrangement in normal individuals: implications for the monitoring of disease in patients with follicular lymphoma. J Clin Oncol 2001; 19: 420424.
  • 29
    Yasukawa M, Bando S, Dolken G, Sada E, Yakushijin Y, Fujita S, et al. Low frequency of BCL-2/J(H) translocation in peripheral blood lymphocytes of healthy Japanese individuals. Blood 2001; 98: 486488.
  • 30
    Fuscoe JC, Setzer RW, Collard DD, Moore MM. Quantification of t(14;18) in the lymphocytes of healthy adult humans as a possible biomarker for environmental exposures to carcinogens. Carcinogenesis 1996; 17: 10131020.
  • 31
    Paltiel O, Zelenetz A, Sverdlin I, Gordon L, Ben-Yehuda D. Translocation t(14;18) in healthy individuals: preliminary study of its association with family history and agricultural exposure. Ann Oncol 2000; 11(Suppl): 7580.
  • 32
    Ladetto M, Drandi D, Compagno M, Astolfi M, Volpato F, Voena C, et al. PCR-detectable nonneoplastic Bcl-2/IgH rearrangements are common in normal subjects and cancer patients at diagnosis but rare in subjects treated with chemotherapy. J Clin Oncol 2003; 21: 13981403.
  • 33
    Gribben JG, Freedman AS, Neuberg D, Roy DC, Blake KW, Woo SD, et al. Immunologic purging of marrow assessed by PCR before autologous bone marrow transplantation for B-cell lymphoma. N Engl J Med 1991; 325: 15251533.
  • 34
    Dolken G, Illerhaus G, Hirt C, Mertelsmann R. BCL-2/JH rearrangements in circulating B cells of healthy blood donors and patients with nonmalignant diseases. J Clin Oncol 1996; 14: 13331344.
  • 35
    Sasso EH, Martinez M, Yarfitz SL, Ghillani P, Musset L, Piette JC, et al. Frequent joining of Bcl-2 to a JH6 gene in hepatitis C virus-associated t(14;18). J Immunol 2004; 173: 35493556.
  • 36
    Sansonno D, Lauletta G, Montrone M, Tucci FA, Dammacco F. Virological and phenotypic analysis of peripheral blood lymphocytes from chronically HCV-infected patients with and without mixed cryoglobulinemia. Clin Exp Immunol 2005; 40. In press.
  • 37
    Curry MP, Golden-Mason L, Doherty DG, Deignan T, Norris S, Duffy M, et al. Expansion of innate CD5pos B cells expressing high levels of CD81 in hepatitis C virus infected liver. J Hepatol 2003; 38: 642650.
  • 38
    Zuckerman E, Kessel A, Slobodin G, Sabo E, Yeshurun D, Toubi E. Antiviral treatment down-regulates peripheral B-cell CD81 expression and CD5 expansion in chronic hepatitis C virus infection. J Virol 2003; 77: 1043210436.
  • 39
    Perl A, Gorevic PD, Ryan DH, Condemi JJ, Ruszkowski RJ, Abraham GN. Clonal B cell expansions in patients with essential mixed cryoglobulinaemia. Clin Exp Immunol 1989; 76: 5460.
  • 40
    Himmelmann A, Gautschi O, Nawrath M, Bolliger U, Fehr J, Stahel RA. Persistent polyclonal B-cell lymphocytosis is an expansion of functional IgD(+)CD27(+) memory B cells. Br J Haematol 2001; 114: 400405.
  • 41
    Troussard X, Flandrin G. Chronic B-cell lymphocytosis with binucleated lymphocytes (LWBL): a review of 38 cases. Leuk Lymphoma 1996; 20: 275279.
  • 42
    Himmelmann A. bcl-2 rearrangement in mixed cryoglobulinemia. Ann Intern Med 2003; 139: 232.
  • 43
    Zhao M, Zhang NX, Economou M, Blaha I, Laissue JA, Zimmermann A. Immunohistochemical detection of bcl-2 protein in liver lesions: bcl-2 protein is expressed in hepatocellular carcinomas but not in liver cell dysplasia. Histopathology 1994; 25: 237245.
  • 44
    Tsamandas AC, Thomopoulos K, Gogos C, Tepetes K, Kourelis T, Ravazoula P, et al. Expresssion of bcl-2 oncoprotein in cases of acute and chronic viral hepatitis type B and type C: a clinicopathologic study. Dig Dis Sci 2002; 47: 16181624.
  • 45
    Casato M, Mecucci C, Agnello V, Fiorilli M, Knight GB, Matteucci C, et al. Regression of lymphoproliferative disorder after treatment for hepatitis C virus infection in a patient with partial trisomy 3, Bcl-2 overexpression, and type II cryoglobulinemia. Blood 2002; 99: 22592261.
  • 46
    Aster JC, Longtine JA. Detection of BCL2 rearrangements in follicular lymphoma. Am J Pathol 2002; 160: 759763.