Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Manuscript
  • Published:

Establishment and comprehensive analysis of a new human transformed follicular lymphoma B cell line, Tat-1

Abstract

A spontaneously EBV transformed follicular lymphoma (FL) cell line, Tat-1, was established from the lymph node biopsy specimen of a patient with B cell FL, grade 1 in transformation to high grade disease. Tat-1 cells expressed lymphoid markers and developed tumor masses in immunodeficient mice. Bcl-2, Bcl-XL, Bax and p53 protein expression was revealed by Western blotting. Flow cytometric analysis confirmed P-gp expression. Cytogenetically, the Tat-1 cell line showed identical chromosomal alterations to that of the initial biopsy specimen, among which the most notable were the t(14;18) typical of FL and additional abnormalities involving chromosomes 1, 8 and 13. Multicolor FISH analysis delineated all abnormalities, including a t(1p;8q), a der(8)(8q24::14q32::18q21) and a der(13)(13q32::8q24::14q32::18q21). Further FISH investigations using a locus-specific probe cocktail containing c-myc, IgH and bcl-2 revealed fusion of these three loci on the derivatives 8 and 13, in addition to the derivative 14 IgH/bcl-2 fusion and an extra copy of c-myc on derivative chromosome 1. These results demonstrate an additional example of the deregulation of bcl-2 and c-myc expression through recombination with a single IgH enhancer region. The unusual molecular features of the Tat-1 cell line render it a unique tool for studies focused on cytogenetic alterations, expression of multidrug resistance phenotype and expression of anti-apoptotic proteins in FL.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  1. Peterson BA . Current treatment of follicular low grade lymphomas Semin Oncol 1999 26: (5 Suppl. 14): 2–11

    Google Scholar 

  2. Gupta RK, Lister TA . Current management of follicular lymphoma Curr Opin Oncol 1996 8: 360–365

    Article  CAS  Google Scholar 

  3. Horning SJ . Treatment approaches to the low-grade lymphomas Blood 1994 83: 881–884

    CAS  PubMed  Google Scholar 

  4. Ludwig CU, Gencik M, Shipman R . Multistep transformation in low-grade lymphoproliferative diseases Ann Oncol 1993 4: 825–830

    Article  CAS  Google Scholar 

  5. Dolcetti R, Boiocchi M . Cellular and molecular basis of B-cell clonal expansions Clini Exp Rheumatol 1996 14 (Suppl. 14): S3–S13

    Google Scholar 

  6. Ilias M, Kendall M, Jalal H, Linton C, Rooney N . Changes in Bcl-2 and p53 expression in recurrent B-cell lymphomas J Pathol 1996 180: 249–253

    Article  Google Scholar 

  7. Soini Y, Raunio H, Paakko P . High-grade malignant non-Hodgkin's lymphomas differ from low-grade lymphomas in the extent of apoptosis and their expression of bcl-2, mcl-1, bax and p53 Tumour Biol 1998 19: 176–185

    Article  CAS  Google Scholar 

  8. Horsman DE, Gascoyne RD, Coupland C, Coldman AJ, Adomat SA . Comparison of cytogenetic analysis, Southern analysis, and polymerase chain reaction for the detection of t(14;18) in follicular lymphoma Am J Clin Pathol 1995 103: 472–478

    Article  CAS  Google Scholar 

  9. Knutsen T . Cytogenetic mechanisms in the pathogenesis and progression of follicular lymphoma Cancer Surv 1997 30: 163–192

    CAS  Google Scholar 

  10. Hockenberry D, Nunez G, Milliman C, Schreiber RD, Korsmeyer SJ . Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death Nature 1990 348: 334–336

    Article  Google Scholar 

  11. McDonnell TJ, Korsmeyer SJ . Progression from lymphoid hyperplasia to high-grade malignant lymphoma in mice transgenic for the t(14;18) Nature 1991 349: 254–256

    Article  CAS  Google Scholar 

  12. Yunis JJ, Frizzera G, Oken MM, McKenna J, Theologides A, Arnesen M . Multiple recurrent genomic defects in follicular lymphoma: a possible model for cancer N Engl J Med 1987 316: 79–84

    Article  CAS  Google Scholar 

  13. Tilly H, Rossi A, Stamatoullas A, Lenormand B, Bigorgne C, Kunlin A, Monconduit M, Bastard C . Prognostic value of chromosomal abnormalities in follicular lymphoma Blood 1994 84: 1043–1049

    CAS  Google Scholar 

  14. Johansson B, Mertens F, Mitelman F . Cytogenetic evolution patterns in non-Hodgkin's lymphoma Blood 1995 86: 3905–3914

    CAS  Google Scholar 

  15. Whang-Peng J, Knutsen T, Jaffe ES, Steinberg SM, Raffeld M, Zhao WP, Duffey P, Condron K, Yano T, Longo DL . Sequential analysis of 43 patients with non-Hodgkin's lymphoma: clinical correlations with cytogenetic histologic immunophenotyping, and molecular studies Blood 1995 85: 203–216

    CAS  PubMed  Google Scholar 

  16. Horsman DE, Connors JM, Pantzar T, Gascoyne RD . Analysis of secondary chromosomal alterations in 165 cases of follicular lymphoma with t(14:18) Genes Chromosomes Cancer 2001 30: 375–382

    Article  CAS  Google Scholar 

  17. Drexler HG, Marsuo Y . Guidelines for the characterization and publication of human malignant hematopoietic cell lines Leukemia 1999 13: 835–842

    Article  CAS  Google Scholar 

  18. Braziel RM, Arber DA, Slovak ML, Gulley ML, Spier C, Kjeldsberg C, Unger J, Miller TP, Tubbs R, Leith C, Fisher RI, Grogan TM . The Burkitt-like lymphomas: a Southwest Oncology Group study delineating phenotypic, genotypic, and clinical features Blood 2001 97: 3713–3720

    Article  CAS  Google Scholar 

  19. Tormo M, Tari AM, McDonnell TJ, Cabanillas F, Garcia-Conde J, Lopez-Berestein G . Apoptotic induction in transformed follicular lymphoma cells by Bcl-2 downregulation Leuk Lymphoma 1998 30: 367–379

    Article  CAS  Google Scholar 

  20. Saati TAI, Delecluze H-J, Chittal S, Brousset P, Magaud J-P, Dastugue N, Cohen-Knafo E, Laurent G, Rubin B, Delsol G . A novel human lymphoma cell line (Deglis) with Dual B/T phenotype and gene rearrangements and containing Epstein–Barr virus genomes Blood 1992 80: 209–216

    PubMed  Google Scholar 

  21. Mitelman F (ed). ISCN An International System for Human Cytogenetic Nomenclature Karger: Basel 1995

    Google Scholar 

  22. Krishna R, De Jong G, Mayer L . Pulsed exposure of SDZ PSC 833 to multidrug resistant P388/ADR and MCF7/ADR cells in the absence of anticancer drugs can fully restore sensitivity to Dox Anticancer Res 1997 17: 3329–3334

    CAS  PubMed  Google Scholar 

  23. Alley MC, Scudiero DA, Monks A, Hursey ML, Czerwinski MJ, Fine DL, Abbott BJ, Mayo JG, Shoemaker RH, Boyd MR . Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay Cancer Res 1998 48: 589–601

    Google Scholar 

  24. Spector DL, Goldman RD, Leinwand LA . Cells. A Laboratory Manual. Volume 1 Culture and Biochemical Analysis of the Cells Cold Spring Harbor Laboratory Press: New York 1998 pp 73.1–73.12

    Google Scholar 

  25. Lee JT, Innes DJ, Williams ME . Sequential bcl-2 and c-myc oncogene rearrangements associated with the clinical transformation of non-Hodgkin's lymphoma J Clin Invest 1989 84: 1454–1459

    Article  CAS  Google Scholar 

  26. Au WY, Gascoyne RD, Viswanatha DS, Skinnider BF, Connors JM, Klasa RJ, Horsman DE . Concurrent chromosomal alterations at 3q27, 8q24 and 18q21 in B-cell lymphomas Br J Haematol 1999 105: 437–440

    Article  CAS  Google Scholar 

  27. Cory S, Vaux DL, Strasser A, Harris AW, Adams AM . Insights from Bcl-2 and Myc: malignancy involves abrogation of apoptosis as well as sustained proliferation Cancer Res 1999 59 (Suppl. 7): 1685s–1692s

    Google Scholar 

  28. van Ooteghem RB, Smit EM, Beishuizen A, Lambrechts AC, vd Blij-Philipsen M, Smilde TJ, Hagemeijer A . A new B-cell line showing a complex translocation (8;14;18) and BCL2 rearrangement Cancer Genet Cytogenet 1994 74: 87–94

    Article  CAS  Google Scholar 

  29. Dyer MJS, Lillington DM, Bastard C, Tilly H, Lens D, Heward JM, Stranks G, Morilla R, Monard S, Guglielmi P, Kluin-Nelemans JC, Hagemeijer A, Young BD, Catovsky D . Concurrent activation of MYC and BCL-2 in B cell non-Hodgkin lymphoma cell lines by translocation of both oncogenes to the same immunoglobulin heavy chain locus Leukemia 1996 10: 1198–1208

    CAS  PubMed  Google Scholar 

  30. Schouten HC, Sanger W, Weisenburger DD, Armitage JO . Abnormalities involving chromosome 6 in newly diagnosed patients with non-Hodgkin's lymphoma Cancer Genet Cytogenet 1990 47: 73–78

    Article  CAS  Google Scholar 

  31. Gaidano G, Hauptschein RS, Parza NZ, Offit K, Rao PH, Lenoir G, Knowles DM, Chaganti RSK, Dalla-Favera R . Deletions involving two distinct regions of 6q in B-cell non-Hodgkin's lymphoma Blood 1992 80: 1781–1787

    CAS  PubMed  Google Scholar 

  32. Chilcote RR, Brown E, Rowley JD . Acute lymphoblastic leukemia with lymphoproliferative features associated with abnormalities of the short arm of chromosome 9 N Engl J Med 1985 313: 286–291

    Article  CAS  Google Scholar 

  33. Hatano M, Roberts CWM, Minden M, Crist WM, Korsmeyer SJ . Deregulation of homeobox gene, HOX11, by the t(10;14) in T cell leukemia Science 1991 253: 79–82

    Article  CAS  Google Scholar 

  34. Hickman JA . Apoptosis and cancer chemotherapy Eur J Cancer 1996 32: 921–926

    Article  Google Scholar 

  35. Nuessler V, Stotzer O, Gullis E, Pelka-Fleischer R, Pogrebniak A, Gieseler F, Wilmanns W . Bcl-2, bax and bcl-xL expression in human sensitive and resistant leukemia cell lines Leukemia 1999 13: 1864–1872

    Article  CAS  Google Scholar 

  36. Findley HW, Gu L, Yeager AM, Zhou M . Expression and regulation of Bcl-2, Bcl-xl, and Bax correlate with p53 status and sensitivity to apoptosis in childhood acute lymphoblastic leukemia Blood 1997 89: 2986–2993

    CAS  PubMed  Google Scholar 

  37. Srinivas G, Kusumakumary P, Nair MK, Panicker KR, Pillai MR . Mutant p53 protein, Bcl-2/Bax ratios and apoptosis in paediatric acute lymphoblastic leukaemia J Cancer Res Clin Oncol 2000 126: 62–67

    Article  CAS  Google Scholar 

  38. Krajewski S, Thor AD, Edgerton SM, Moore DH, Krajewska M, Reed JC . Analysis of Bax and Bcl-2 expression in p53-immunopositive breast cancers Clin Cancer Res 1997 3: 199–208

    CAS  PubMed  Google Scholar 

  39. Miyashita T, Harigai M, Hanada M, Reed JC . Identification of a p53-dependent negative response element in the bcl-2 gene Cancer Res 1994 54: 3131–3135

    CAS  PubMed  Google Scholar 

  40. Miyashita T, Krajewski S, Krajewska M, Wang HG, Lin HK, Liebermann DA, Hoffman B, Reed JC . Tumor suppressor p53 is aregulator of bcl-2 and bax gene expression in vitro and in vivo Oncogene 1994 9: 1799–1805

    CAS  PubMed  Google Scholar 

  41. Miyashita T, Reed JC . Tumor suppressor p53 is a direct transcriptional activator of the human bax gene Cell 1995 80: 293–299

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by The National Cancer Institute of Canada with funds from the Canadian Cancer Society. We are very grateful to Don Philips, Kees Pot and Visia Dragovska for technical assistance in flow cytometric analysis, Dana Masin for animal work assistance and Dr Chris Williams for clinical care of the patient.

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Denyssevych, T., Lestou, V., Knesevich, S. et al. Establishment and comprehensive analysis of a new human transformed follicular lymphoma B cell line, Tat-1. Leukemia 16, 276–283 (2002). https://doi.org/10.1038/sj.leu.2402372

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2402372

Keywords

This article is cited by

Search

Quick links