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Establishment of a CD4-positive cell line from an AIDS-related primary effusion lymphoma

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Abstract

Primary effusion lymphoma (PEL) presents as a serous lymphomatous effusion without tumor masses exclusively in body cavities and mainly occurs in human immunodeficiency virus-1 (HIV-1)-infected patients. We established a new PEL cell line, designated GTO, from the pericardial effusion of a 39-year-old Japanese patient with acquired immunodeficiency syndrome-related PEL. This cell line was infected with human herpesvirus-8, but not with Epstein–Barr virus. Southern blot hybridization demonstrated that GTO cells display monoclonal rearrangement of the IgH gene, suggesting clonal B cell proliferation. GTO cells weakly express or lack T cell-associated markers (CD3, CD5, CD8), the majority of B cell-associated markers (CD19, CD20, CD21, CD79a), the α chains of β 2 integrins (CD11a, CD11b, CD11c), HLA-DR, CD30, and surface immunoglobulin (sIgM, sIgG sIgκ, sIgλ), TCR (α/β, γδ), but express CD45, and post-germinal center B cell/plasma cell-associated antigens (CD38, CD138). They also express a high level of cell-surface CD4 and can be infected by HIV-1. Immunodeficient mice intraperitoneally xenografted with GTO cells developed ascites containing lymphoma cells. The establishment of GTO and a GTO xenograft mouse model may help to provide insights toward a better understanding of the pathogenesis of PEL and the relationship between HIV-1 and HHV-8.

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References

  1. Nador RG, Cesarman E, Chadburn A, Dawson DB, Ansari MQ, Sald J, et al. Primary effusion lymphoma: a distinct clinicopathologic entity associated with the Kaposi’s sarcoma-associated herpes virus. Blood. 1996;88:645–56.

    PubMed  CAS  Google Scholar 

  2. Cesarman E, Nador RG, Bai F, Bohenzky RA, Russo JJ, Moore PS, et al. Kaposi’s sarcoma-associated herpesvirus contains G protein-coupled receptor and cyclin D homologs which are expressed in Kaposi’s sarcoma and malignant lymphoma. J Virol. 1996;70:8218–23.

    PubMed  CAS  Google Scholar 

  3. Cesarman E, Chang Y, Moore PS, Said JW, Knowles DM. Kaposi’s sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas. New Eng J Med. 1995;332:1186–91.

    Article  PubMed  CAS  Google Scholar 

  4. Carbone A, Gaidano G. HHV-8-positive body-cavity-based lymphoma: a novel lymphoma entity. Br J Haematol. 1997;97:515–22.

    Article  PubMed  CAS  Google Scholar 

  5. Merat R, Amara A, Lebbe C, de The H, Morel P, Saib A. HIV-1 infection of primary effusion lymphoma cell line triggers Kaposi’s sarcoma-associated herpesvirus (KSHV) reactivation. Int J Cancer. 2002;97:791–5.

    Article  PubMed  CAS  Google Scholar 

  6. Zhu X, Zhou F, Qin D, Zeng Y, Lv Z, Yao S, et al. Human immunodeficiency virus type 1 induces lytic cycle replication of Kaposi’s-sarcoma-associated herpesvirus: role of Ras/c-Raf/MEK1/2, PI3 K/AKT, and NF-kappaB signaling pathways. J Mol Biol. 2011;410:1035–51.

    Article  PubMed  CAS  Google Scholar 

  7. Drexler HG, Matsuo Y. Guidelines for the characterization and publication of human malignant hematopoietic cell lines. Leukemia. 1999;13:835–42.

    Article  PubMed  CAS  Google Scholar 

  8. Renne R, Zhong W, Herndier B, McGrath M, Abbey N, Kedes D, et al. Lytic growth of Kaposi’s sarcoma-associated herpesvirus (human herpesvirus 8) in culture. Nat Med. 1996;2:342–6.

    Article  PubMed  CAS  Google Scholar 

  9. Cesarman E, Moore PS, Rao PH, Inghirami G, Knowles DM, Chang Y. In vitro establishment and characterization of two acquired immunodeficiency syndrome-related lymphoma cell lines (BC-1 and BC-2) containing Kaposi’s sarcoma-associated herpesvirus-like (KSHV) DNA sequences. Blood. 1995;86:2708–14.

    PubMed  CAS  Google Scholar 

  10. Arvanitakis L, Mesri EA, Nador RG, Said JW, Asch AS, Knowles DM, et al. Establishment and characterization of a primary effusion (body cavity-based) lymphoma cell line (BC-3) harboring kaposi’s sarcoma-associated herpesvirus (KSHV/HHV-8) in the absence of Epstein-Barr virus. Blood. 1996;88:2648–54.

    PubMed  CAS  Google Scholar 

  11. Katano H, Hoshino Y, Morishita Y, Nakamura T, Satoh H, Iwamoto A, et al. Establishing and characterizing a CD30-positive cell line harboring HHV-8 from a primary effusion lymphoma. J Med Virol. 1999;58:394–401.

    Article  PubMed  CAS  Google Scholar 

  12. Pulvertaft JV. Cytology of Burkitt’s Tumour (African Lymphoma). Lancet. 1964;1:238–40.

    Article  PubMed  CAS  Google Scholar 

  13. Boshoff C, Gao SJ, Healy LE, Matthews S, Thomas AJ, Coignet L, et al. Establishing a KSHV + cell line (BCP-1) from peripheral blood and characterizing its growth in Nod/SCID mice. Blood. 1998;91:1671–9.

    PubMed  CAS  Google Scholar 

  14. Miyagi J, Masuda M, Takasu N, Nagasaki A, Shinjyo T, Uezato H, et al. Establishment of a primary effusion lymphoma cell line (RM-P1) and in vivo growth system using SCID mice. Int J Hematol. 2002;76:165–72.

    Article  PubMed  CAS  Google Scholar 

  15. Miller G, Heston L, Grogan E, Gradoville L, Rigsby M, Sun R, et al. Selective switch between latency and lytic replication of Kaposi’s sarcoma herpesvirus and Epstein-Barr virus in dually infected body cavity lymphoma cells. J Virol. 1997;71:314–24.

    PubMed  CAS  Google Scholar 

  16. Klass CM, Krug LT, Pozharskaya VP, Offermann MK. The targeting of primary effusion lymphoma cells for apoptosis by inducing lytic replication of human herpesvirus 8 while blocking virus production. Blood. 2005;105:4028–34.

    Article  PubMed  CAS  Google Scholar 

  17. Shaffer LG, Tommerup N, International Standing Committee on Human Cytogenetic Nomenclature. ISCN 2005: an international system for human cytogenetic nomenclature (2005): recommendations of the International Standing Committee on Human Cytogenetic Nomenclature. Basel: Karger; 2005.

    Google Scholar 

  18. Uhara H, Sato Y, Mukai K, Akao I, Matsuno Y, Furuya S, et al. Detection of Epstein-Barr virus DNA in Reed-Sternberg cells of Hodgkin’s disease using the polymerase chain reaction and in situ hybridization. Jap J Cancer Res: Gann. 1990;81:272–8.

    Article  CAS  Google Scholar 

  19. Krishnan HH, Naranatt PP, Smith MS, Zeng L, Bloomer C, Chandran B. Concurrent expression of latent and a limited number of lytic genes with immune modulation and antiapoptotic function by Kaposi’s sarcoma-associated herpesvirus early during infection of primary endothelial and fibroblast cells and subsequent decline of lytic gene expression. J Virol. 2004;78:3601–20.

    Article  PubMed  CAS  Google Scholar 

  20. Bechtel J, Grundhoff A, Ganem D. RNAs in the virion of Kaposi’s sarcoma-associated herpesvirus. J Virol. 2005;79:10138–46.

    Article  PubMed  CAS  Google Scholar 

  21. Ota K, Fujimori H, Ueda M, Shiniriki S, Kudo M, Jono H, et al. Midkine as a prognostic biomarker in oral squamous cell carcinoma. Br J Cancer. 2008;99:655–62.

    Article  PubMed  CAS  Google Scholar 

  22. Koyanagi Y, Miles S, Mitsuyasu RT, Merrill JE, Vinters HV, Chen IS. Dual infection of the central nervous system by AIDS viruses with distinct cellular tropisms. Science. 1987;236:819–22.

    Article  PubMed  CAS  Google Scholar 

  23. Goto H, Kariya R, Shimamoto M, Kudo E, Taura M, Katano H, et al. Antitumor effect of berberine against primary effusion lymphoma via inhibition of NF-kappaB pathway. Cancer Sci. 2012;103:775–81.

    Article  PubMed  CAS  Google Scholar 

  24. Drexler HG, Uphoff CC, Gaidano G, Carbone A. Lymphoma cell lines: in vitro models for the study of HHV-8+ primary effusion lymphomas (body cavity-based lymphomas). Leukemia. 1998;12:1507–17.

    Article  PubMed  CAS  Google Scholar 

  25. Sun R, Lin SF, Gradoville L, Yuan Y, Zhu F, Miller G. A viral gene that activates lytic cycle expression of Kaposi’s sarcoma-associated herpesvirus. Proc Natl Acad Sci USA. 1998;95:10866–71.

    Article  PubMed  CAS  Google Scholar 

  26. Lukac DM, Kirshner JR, Ganem D. Transcriptional activation by the product of open reading frame 50 of Kaposi’s sarcoma-associated herpesvirus is required for lytic viral reactivation in B cells. J Virol. 1999;73:9348–61.

    PubMed  CAS  Google Scholar 

  27. Beral V, Peterman T, Berkelman R, Jaffe H. AIDS-associated non-Hodgkin lymphoma. Lancet. 1991;337:805–9.

    Article  PubMed  CAS  Google Scholar 

  28. Carbone A, Cesarman E, Spina M, Gloghini A, Schulz TF. HIV-associated lymphomas and gamma-herpesviruses. Blood. 2009;113:1213–24.

    Article  PubMed  CAS  Google Scholar 

  29. Katano H, Iwasaki T, Baba N, Terai M, Mori S, Iwamoto A, et al. Identification of antigenic proteins encoded by human herpesvirus 8 and seroprevalence in the general population and among patients with and without Kaposi’s sarcoma. J Virol. 2000;74:3478–85.

    Article  PubMed  CAS  Google Scholar 

  30. Katano H, Sata T. Human herpesvirus 8 virology, epidemiology and related diseases. Jpn J Infect Dis. 2000;53:137–55.

    PubMed  CAS  Google Scholar 

  31. Carbone A, Cesarman E, Gloghini A, Drexler HG. Understanding pathogenetic aspects and clinical presentation of primary effusion lymphoma through its derived cell lines. AIDS. 2010;24:479–90.

    Article  PubMed  Google Scholar 

  32. Inaba T, Shimazaki C, Sumikuma T, Okano A, Hatsuse M, Okamoto A, et al. Expression of T-cell-associated antigens in B-cell non-Hodgkin’s lymphoma. Br J Haematol. 2000;109:592–9.

    Article  PubMed  CAS  Google Scholar 

  33. Kaleem Z, White G, Zutter MM. Aberrant expression of T-cell-associated antigens on B-cell non-Hodgkin lymphomas. Am J Clin Pathol. 2001;115:396–403.

    Article  PubMed  CAS  Google Scholar 

  34. Blasig C, Zietz C, Haar B, Neipel F, Esser S, Brockmeyer NH, et al. Monocytes in Kaposi’s sarcoma lesions are productively infected by human herpesvirus 8. J Virol. 1997;71:7963–8.

    PubMed  CAS  Google Scholar 

  35. Monini P, Colombini S, Sturzl M, Goletti D, Cafaro A, Sgadari C, et al. Reactivation and persistence of human herpesvirus-8 infection in B cells and monocytes by Th-1 cytokines increased in Kaposi’s sarcoma. Blood. 1999;93:4044–58.

    PubMed  CAS  Google Scholar 

  36. Moir S, Lapointe R, Malaspina A, Ostrowski M, Cole CE, Chun TW, et al. CD40-Mediated induction of CD4 and CXCR4 on B lymphocytes correlates with restricted susceptibility to human immunodeficiency virus type 1 infection: potential role of B lymphocytes as a viral reservoir. J Virol. 1999;73:7972–80.

    PubMed  CAS  Google Scholar 

  37. Roy D, Sin SH, Damania B, Dittmer DP. Tumor suppressor genes FHIT and WWOX are deleted in primary effusion lymphoma (PEL) cell lines. Blood. 2011;118:e32–9.

    Article  PubMed  Google Scholar 

  38. Wilson KS, McKenna RW, Kroft SH, Dawson DB, Ansari Q, Schneider NR. Primary effusion lymphomas exhibit complex and recurrent cytogenetic abnormalities. Br J Haematol. 2002;116:113–21.

    Article  PubMed  Google Scholar 

  39. Fan W, Bubman D, Chadburn A, Harrington WJ Jr, Cesarman E, Knowles DM. Distinct subsets of primary effusion lymphoma can be identified based on their cellular gene expression profile and viral association. J Virol. 2005;79:1244–51.

    Article  PubMed  CAS  Google Scholar 

  40. Mack AA, Sugden B. EBV is necessary for proliferation of dually infected primary effusion lymphoma cells. Cancer Res. 2008;68:6963–8.

    Article  PubMed  CAS  Google Scholar 

  41. Staudt MR, Kanan Y, Jeong JH, Papin JF, Hines-Boykin R, Dittmer DP. The tumor microenvironment controls primary effusion lymphoma growth in vivo. Cancer Res. 2004;64:4790–9.

    Article  PubMed  CAS  Google Scholar 

  42. Ito M, Hiramatsu H, Kobayashi K, Suzue K, Kawahata M, Hioki K, et al. NOD/SCID/gamma(c)(null) mouse: an excellent recipient mouse model for engraftment of human cells. Blood. 2002;100:3175–82.

    Article  PubMed  CAS  Google Scholar 

  43. Okada S, Harada H, Ito T, Saito T, Suzu S. Early development of human hematopoietic and acquired immune systems in new born NOD/Scid/Jak3null mice intrahepatic engrafted with cord blood-derived CD34 + cells. Int J Hematol. 2008;88:476–82.

    Article  PubMed  Google Scholar 

  44. Dewan MZ, Terunuma H, Toi M, Tanaka Y, Katano H, Deng X, et al. Potential role of natural killer cells in controlling growth and infiltration of AIDS-associated primary effusion lymphoma cells. Cancer Sci. 2006;97:1381–7.

    Article  PubMed  CAS  Google Scholar 

  45. Chadburn A, Hyjek E, Mathew S, Cesarman E, Said J, Knowles DM. KSHV-positive solid lymphomas represent an extra-cavitary variant of primary effusion lymphoma. Am J Surg Pathol. 2004;28:1401–16.

    Article  PubMed  Google Scholar 

  46. Carbone A, Gloghini A, Vaccher E, Cerri M, Gaidano G, Dalla-Favera R, et al. Kaposi’s sarcoma-associated herpesvirus/human herpesvirus type 8-positive solid lymphomas: a tissue-based variant of primary effusion lymphoma. J Mol Diagn. 2005;7:17–27.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank Ms. I. Suzu and Ms. S. Fujikawa for technical assistance and Ms. K. Tokunaga for secretarial assistance. This work was supported in part by a Health and Labour Sciences Research Grant from the Ministry of Health, Labour, and Welfare of Japan (H22-AIDS-I-002), by the Global COE program, “Global Education and Research Center Aiming at the Control of AIDS”, and Grants-in-Aid for Science Research (No. 23107725) from the Ministry of Education, Science, Sports, and Culture of Japan.

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Correspondence to Seiji Okada.

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Goto, H., Kojima, Y., Nagai, H. et al. Establishment of a CD4-positive cell line from an AIDS-related primary effusion lymphoma. Int J Hematol 97, 624–633 (2013). https://doi.org/10.1007/s12185-013-1339-3

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  • DOI: https://doi.org/10.1007/s12185-013-1339-3

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