Studies on the oncogenic potential of epstein-barr-virus (EBV)-infected B cells in aids-related disorders
Corresponding Author
Silvio Roncella
Servizio di Immunologia Clinica, Istituto Nazionale per la Ricerca sul Cancro, IST Genoa
Servizio di Immunologia Clinica, Istituto Nazionale per la Ricerea sul Cancro, IST, Viale Benedetto XV, 10, 16132 Genoa, ItalySearch for more papers by this authorPatrizia Caretto
Istituto di Microbiologia, Universitæ di Torino, Turin
Search for more papers by this authorGuido Forni
Istituto di Microbiologia, Universitæ di Torino, Turin
Search for more papers by this authorGiovanna Cutrona
Servizio di Immunologia Clinica, Istituto Nazionale per la Ricerca sul Cancro, IST Genoa
Search for more papers by this authorAntimo Verde
Servizio di Immunologia Clinica, Istituto Nazionale per la Ricerca sul Cancro, IST Genoa
Search for more papers by this authorDunia Ramarli
Servizio di Immunobiologia, Istituto Nazionale per la Ricerca sul Cancro, IST Genoa
Search for more papers by this authorPaola Francia Di Celle
Dipartimento di Scienze Biomediche ed Oncologia Umana, Università di Torino, Turin
Search for more papers by this authorRobin Foà
Dipartimento di Scienze Biomediche ed Oncologia Umana, Università di Torino, Turin
Search for more papers by this authorMario Sessarego
Istituto Scientifico di Medicina Interna, Università di Genova, Genoa
Search for more papers by this authorVito Pistoia
Servizio di Immunologia Clinica, Istituto Nazionale per la Ricerca sul Cancro, IST Genoa
Istituto di Oncologia Clinica e Sperimentale, Università di Genova, Genoa, Italy
Search for more papers by this authorManlio Ferrarini
Servizio di Immunologia Clinica, Istituto Nazionale per la Ricerca sul Cancro, IST Genoa
Dipartimento di Scienze Biomediche ed Oncologia Umana, Università di Torino, Turin
Search for more papers by this authorCorresponding Author
Silvio Roncella
Servizio di Immunologia Clinica, Istituto Nazionale per la Ricerca sul Cancro, IST Genoa
Servizio di Immunologia Clinica, Istituto Nazionale per la Ricerea sul Cancro, IST, Viale Benedetto XV, 10, 16132 Genoa, ItalySearch for more papers by this authorPatrizia Caretto
Istituto di Microbiologia, Universitæ di Torino, Turin
Search for more papers by this authorGuido Forni
Istituto di Microbiologia, Universitæ di Torino, Turin
Search for more papers by this authorGiovanna Cutrona
Servizio di Immunologia Clinica, Istituto Nazionale per la Ricerca sul Cancro, IST Genoa
Search for more papers by this authorAntimo Verde
Servizio di Immunologia Clinica, Istituto Nazionale per la Ricerca sul Cancro, IST Genoa
Search for more papers by this authorDunia Ramarli
Servizio di Immunobiologia, Istituto Nazionale per la Ricerca sul Cancro, IST Genoa
Search for more papers by this authorPaola Francia Di Celle
Dipartimento di Scienze Biomediche ed Oncologia Umana, Università di Torino, Turin
Search for more papers by this authorRobin Foà
Dipartimento di Scienze Biomediche ed Oncologia Umana, Università di Torino, Turin
Search for more papers by this authorMario Sessarego
Istituto Scientifico di Medicina Interna, Università di Genova, Genoa
Search for more papers by this authorVito Pistoia
Servizio di Immunologia Clinica, Istituto Nazionale per la Ricerca sul Cancro, IST Genoa
Istituto di Oncologia Clinica e Sperimentale, Università di Genova, Genoa, Italy
Search for more papers by this authorManlio Ferrarini
Servizio di Immunologia Clinica, Istituto Nazionale per la Ricerca sul Cancro, IST Genoa
Dipartimento di Scienze Biomediche ed Oncologia Umana, Università di Torino, Turin
Search for more papers by this authorAbstract
Spontaneous lymphoblastoid cell lines (LCLs) were established from the peripheral blood of 10 human immunodeficiency virus (HIV)-seropositive patients in order to investigate whether or not progression of the cells towards a malignant state could be traced. The LCLs studied displayed no differences in their surface phenotype, karyotype, and tumorigenicity in nude mice as compared with a wide panel of control LCLs. Furthermore, no c-myc rearrangement could be detected in any of the LCLs. However, 4 of the 10 LCLs derived from HIV-seropositive patients formed colonies in agar with a cloning efficiency of 0.1–0.9%. This percentage was much lower than that of a control neoplastic B cell line (50%), but consistently higher than that observed for a battery of spontaneous LCLs. The cells of a number of sublines that were derived from the agar colonies expressed new activation markers (CD10 and Bac-I) but did not induce tumors in nude mice or display chromosomal abnormalities. These sublines might comprise cells that have progressed towards a more markedly transformed state.
References
- Alonso, L., Richardson, M. E., Metroka, C. E., Movradian, J. A., Kodurn, P. R. K., Filippa, D. A. and Chaganti, R. S. K., Chromosome abnormalities in AIDS-associated lymphadenopathy. Blood, 69, 855–858 (1987).
- Arione, R., Jemma, C., Forni, M., Marchese, C., Benetton, G., Giubellino, C., Modesti, A., Martinotti, M. G., Cordero di Montezemolo, L., Musso, L. and Forni, G., A new child T-cell lymphoma established in nude mice and in vitro. Cancer Res., 48, 1312–1318 (1988).
- Birx, D. L., Redfield, R. R. and Tosato, G., Defective regulation of Epstein-Barr-virus infection in patients with acquired immunodeficiency-syndrome (AIDS) or AIDS-related disorders. New Engl. J. Med., 314, 874–879 (1986).
- Caspersson, T., Zech C., Johansson, C. and Modest, E., Identification of human chromosome by DNA binding fluorescing agents. Chromosoma, 30, 215–227 (1970).
- Centers for disease control. Update: acquired immune-deficiency syndrome (AIDS), United States. M. M. W. R. 33, 337–341 (1984).
- Cleary, M. L., Warnke, R. and Sklar, J., Monoclonality of lymphoproliferative lesions in cardiac-transplant recipients: clonal analysis based on immunoglobulin-gene rearrangements. New Engl. J. Med., 310, 477–482 (1984).
- Croce, C. M. and Nowell, P., Molecular basis of human B-cell neoplasia. Blood. 65, 1–7 (1985).
-
Faucl, A. S.,
Macher, A. B. and
Longo, D. L.,
Acquired immunodeficiency syndrome: epidemiologic, clinical, immunologic and therapeutic considerations.
Ann. int. Med.,
100,
92–106
(1984).
10.7326/0003-4819-100-1-92 Google Scholar
- Groopman, J. E., Sullivan, J. L., Mulder, C., Ginsburg, D., Orkin, S. H., O'Hara, C. S., Falchuk, K., Wong-Staal, F. and Gallo, R. C., Pathogenesis of B-cell lymphoma in a patient with AIDS. Blood, 67, 612–615 (1986).
- Guerrasio, A., Avanzi, G. C., Pegoraro, L., Estivili, X., Serra, A., Giubellino, M. C., Fierro, M. T., Novarino, A., Foa, R. and Saglio, G. Rearrangement of the c-myc oncogene with heavy-chain immunoglobulin enhancer in tumor DNA from an acute lymphoblastic leukemia patient. J. nat. Canc. Inst., 78, 845–849 (1987).
- Henle, W., Henle, G. and Horwitz, C. A., Epstein-Barr-virus diagnostic tests in infectious mononucleosis. Hum. Pathol., 5, 551–565 (1974).
- Holt, J. T., Morton, C. C., Nienhuis, A. W. and Leder, P., Molecular mechanisms of hematological neoplasms. In: G. Stamatoyannopoulos, A. W. Nienhuis, P. Leder and P. W. Majerus (eds.), The molecular basis of blood diseases, pp. 347–376, W. B. Saunders, Philadelphia (1987).
- Knowles, D. M., Chamulak, G. A., Subar, M., Burke, J. S., Dugan, M., Weruz, J., Seywotzky, C., Pellicci, P. G., Dalla Favera, R. and Raphael, B., Lymphoid neoplasia associated with the acquired immunodeficiency syndrome (AIDS): the New York University Medical Center experience with 105 patients (1981-1986). Ann int. Med., 108, 744–753 (1988).
- Levine, A. A., Meyer, P. R., Begandy, M. K., Parker, J. N., Taylor, C. R., Irwing, L. and Lukes, R. J., Development of B-cell lymphoma in homosexual men. Ann. int. Med., 100, 7–12 (1984).
- List, A. F., Greco, F. A. and Vogler, L. B., Lymphoproliferative diseases in immunocompromised host: the role of Epstein-Barr virus. J. clin. Oncol., 51, 1673–1689 (1987).
- Lombardi, L., Newcomb, E. W. and Dalla Favera, R., Pathogenesis of Burkitt lymphoma: expression of an activated c-myc oncogene causes the tumorigenic conversion of EBV-injected human B lymphoblasts. Cell, 49, 161–170 (1987).
-
Lowenthal, D. A.,
Straus, D. J.,
Campbell, S. W.,
Gold, J. W.,
Clarkson, B. D. and
Koziner, B.,
AIDS-related lymphoid neoplasia. The Memorial Hospital experience.
Cancer,
61,
2325–2337
(1988).
10.1002/1097-0142(19880601)61:11<2325::AID-CNCR2820611130>3.0.CO;2-0 CAS PubMed Web of Science® Google Scholar
- Nilsson, K. and Ponten, J., Classification and biological nature of established human hematopoietic cell lines. Int. J. Cancer, 15, 321–341 (1975).
- Pelicci, P. G., Knowles, D. M., Magrath, T. and Dalla Favera, R., Chromosomal breakpoints and structural alterations of the c-myc locus differ in endemic and sporadic forms of Burkitt lymphoma. Proc. nat. Acad. Sci. (Wash.), 83, 2984–2988 (1986).
- Peterson, J. M., Tubbs, R. R., Savage, R. A., Calabrese, R. C., Profitt, M. R., Mandova, Y., Mandov, G., Shumaker, A., Tatsumi, E., McLain, K. and Purtilo, D. T., Small non-cleaved B-cell Burkitt-like lymphoma with chromosome t (8:14) translocation and Epstein-Barr-virus nuclear-associated antigen in a homosexual male with acquired immunodeficiency syndrome. Amer. J. Med., 78, 141–148 (1985).
- Pike, B. L. and Robinson, W. A., Human bone-marrow colony growth in agar gel. J. Cell Physiol., 76, 77–84 (1970).
- Pistoia, V., Ghio, R., Roncella, S., Cozzolino, F., Zupo, S. and Ferrarini, M., Production of colony-stimulating activity by normal and neoplastic human B lymphocytes. Blood, 69, 1340–1347 (1987).
- Posnett, D. N., Chiorazzi, N. and Kunkel, H. G., Monoclonal antibodies with specificity for hairy-cell leukemia cells. J. clin. Invest., 70, 254–259 (1982).
- Rechavi, G., Ben-Bassat, I., Berkowicz, M., Martinowitz, V., Brok-Simoni, F., Neumann, Y., Vansover, A., Gotlieb-Stematsky, T. and Ramot, B., Molecular analysis of Burkitt's leukemia in two hemophilic brothers with AIDS. Blood, 70, 1713–1717 (1987).
- Rowe, M., Hildreth, J. E. K., Rickinson, A. B. and Epstein, M. A., Monoclonal antibodies to Epstein-Barr-virus-induced, transformation-associated cell surface antigens: binding patterns and effect upon virus-specific T-cell cytotoxicity. Int. J. Cancer, 29, 373–381 (1982).
- Rowe, M., Rowe, D. T., Gregory, C. D., Young, L. S., Farrell, P. J., Ripani, H. and Rickinson, A. B., Differences in B-cell growth phenotype reflect novel patterns of Epstein-Barr-virus latent gene expression in Burkitt's lymphoma cells. EMBO J., 6, 2743–2751 (1987).
- Sandberg, A. A., Chromosomes in leukemia and cancer, p. 143, Elsevier, New York (1980).
- Seremetis, S., Inghirami, G., Ferrero, D., Newcomb, E. W., Knowles, D. M., Dotto, G. P. and Dalla Favera, R., Transformation and plasmacytoid differentiation of EBV-infected human lymphoblasts by ras oncogenes. Science, 243, 660–663 (1989).
- Subar, M., Neri, A., Inghirami, G., Knowles, D. M. and Dalla Favera, R., Frequent myc oncogene activation and infrequent presence of Epstein-Barr-virus genome in AIDS-associated lymphoma. Blood, 72, 667–671 (1988).
- Suzuki, T., Sanders, S. K., Butler, J. L., Gartland, G. L., Komiyama, K. and Cooper, M. D., Identification of an early activation antigen (Bac-1) on human B cells. Cells, 137, 1208–1213 (1986).
- Thorley-Lawson, D. A., Nadler, L. M., Bhan, A. K. and Schooley, R. T., Blast-2 (EBVCS), an early cell surface marker of human B-cell activation is superinduced by Epstein-Barr virus. J. Immunol., 134, 3007–3012 (1985).
- Tosato, G., The Epstein-Barr virus and the immune system. Adv. Cancer Res., 49, 75–125 (1987).
- Whang-Peng, J., Lee, E. C., Sieverts, H. and Magrath, I. T., Burkitt's lymphoma in AIDS. Cytogenetic studies. Blood, 63, 818–822 (1984).
