Advertisement

Medical Oncology

, Volume 12, Issue 3, pp 167–176 | Cite as

Molecular pathology of low grade malignant lymphomas

  • Howard Ratech
Article

Abstract

During the last ten years the combined efforts of pathologists and molecular biologists have helped define several new lymphoma diagnostic categories. In particular, the recognition of chromosomal translocations which have activated the BCL1 and BCL2 proto-oncogenes have strong associations with specific types of non-Hodgkin’s malignant lymphomas such as mantle cell lymphoma and follicular center cell lymphoma, respectively. This review will attempt to summarize our current understanding regarding the contributions of BCL1 and BCL2 to lymphomagenesis and diagnosis.

Keywords

lymphoma BCL1 BCL2 mantle cell lymphoma follicular lymphoma molecular diagnosis DNA 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    The non-Hodgkin’s lymphoma pathologic classification project. (1982) National Cancer Institute sponsored study of classifications of non-Hodgkin’s lymphomas. Summary and description of a Working Formulation for clinical usage.Cancer 49, 2112–35.CrossRefGoogle Scholar
  2. 2.
    Harris, N.L., Jaffe, E.S., Stein, H., Banks, P.M., Chan, J.K.C., Cleary, M.L., Delsol, G., De Wolf-Peeters, C., Falini, B., Gatter, K.C., Grogan, T.M., Isaacson, P.G., Knowles, D.M., Mason, D.Y., Muller-Hermelink, H.-K., Pileri, S.A., Piris, M.A., Ralfkiaer, E. and Warnke, R. (1994) A revised European-American classification of lymphoid neoplasms: A proposal from the International Lymphoma Study Group.Blood 84, 1361–92.PubMedGoogle Scholar
  3. 3.
    Nowell, P. (1992) Cancer, chromosomes, and genes.Laboratory Investigation 66, 407–17.PubMedGoogle Scholar
  4. 4.
    Ratech, H. (1993) The uses of molecular biology in hematopathology. Oncogenes as diagnostic markers in non-Hodgkin’s malignant lymphoma.American Journal of Clinical Pathology 99, 381–4.PubMedGoogle Scholar
  5. 5.
    Erikson, J., Finan, J., Tsujimoto, Y., Nowell, P.C. and Croce, C.M. (1984) The chromosome 14 breakpoint in neoplastic B cells with the t(11;14) translocation involves the immunoglobulin heavy chain locus.Proceedings National Academy of Sciences USA 81, 4144–48.CrossRefGoogle Scholar
  6. 6.
    Tsujimoto, Y., Jaffe, E., Cossman, J., Gorham, J., Nowell, P.C. and Croce, C.M. (1985) Clustering of breakpoints on chromosome 11 in human B-cell neoplasms with the t(11;14) chromosome translocation.Nature 315, 340–3.PubMedCrossRefGoogle Scholar
  7. 7.
    Tsujimoto, Y., Yunis, J., Onorato-Showe, L., Erikson, J., Nowell, P.C. and Croce, C.M. (1984) Molecular cloning of the chromosomal breakpoint of B-cell lymphomas and leukemias with the t(11;14) chromosome translocation.Science 224, 1403–6.PubMedCrossRefGoogle Scholar
  8. 8.
    Abe, M., Nozawa, Y., Wakasa, H., Ohno, H. and Fukuhara, S. (1988) Characterization and comparison of two newly established Epstein-Barr virus-negative lymphoma B-cell lines. Surface markers, growth characteristics, cytogenetics, and transplantability.Cancer 61, 483–90.PubMedCrossRefGoogle Scholar
  9. 9.
    Barlogie, B. and Alexanian, R. (1987) Biology and therapy of multiple myeloma.Acta Hematol (Suppl 1),78, 171–4.Google Scholar
  10. 10.
    Chaganti, R. and Koduru, P. (1987) Patterns of chromosome breakage in nonHodgkin lymphoma: Significance to gene alteration in tumorigenesis.Cytogenetics Cell Genetics 45, 93–8.CrossRefGoogle Scholar
  11. 11.
    Fukuhara, S., Rowley, J., Variakojis, D. and Golomb, H. (1979) Chromosome abnormalities in poorly differentiated lymphocytic lymphoma.Cancer Res. 39, 3119–28.PubMedGoogle Scholar
  12. 12.
    Van Den Berghe, H., Parloir, C., David, G., Michaux, J. and Sokal, G. (1979) A new characteristic karyotypic anomaly in lymphoproliferative disorders.Cancer 44, 188–95.CrossRefGoogle Scholar
  13. 13.
    Yunis, J. (1983) The chromosomal basis of human neoplasia.Science 221, 227–36.PubMedCrossRefGoogle Scholar
  14. 14.
    Meeker, T.C., Jr., Grimaldi, J.C., O’Rourke, R., Louie, E., Juliusson, G. and Einhorn, S. (1989) An additional break-point region in the BCL-1 locus associated with the t(11;14) translocation of B-lymphocytic malignancy.Blood 74, 1801–6.PubMedGoogle Scholar
  15. 15.
    Rabbitts, P.H., Douglas, J., Fischer, P., Nacheva, E., Karpas, A., Catovsky, D., Melo, J.V., Baer, R., Stinson, M.A. and Rabbitts, T.H. (1988) Chromosome abnormalities at 11q13 in B cell tumors.Oncogene 3, 99–103.Google Scholar
  16. 16.
    Medeiros, L.J., van Krieken, J.H., Jaffe, E.S. and Raffield, M. (1990) Association of bcl-1 rearrangements with lymphocytic lymphoma of intermediate differentiation.Blood 76, 2086–90.PubMedGoogle Scholar
  17. 17.
    Williams, M.E., Westermann, C.D. and Swerdlow, S.H. (1990) Genotypic characterization of centrocytic lymphoma: frequent rearrangement of the chromosome 11 bcl-1 locus.Blood 76, 1387–91.PubMedGoogle Scholar
  18. 18.
    Raghoebier, S., van Krieken, J.H., Kluin-Nelemans, J.C., Gillis, A., van Ommen, G.J., Ginsberg, A.M., Raffeld, M. and Kluin, P.M. (1991) Oncogene rearrangements in chronic B-cell leukemia.Blood 77, 1560–64.PubMedGoogle Scholar
  19. 19.
    Weisenburger, D.D., Sanger, W.G., Armitage, J.O. and Purtilo, D.T. (1987) Intermediate lymphocytic lymphoma: immunophenotypic and cytogenetic findings.Blood 69, 1617–21.PubMedGoogle Scholar
  20. 20.
    Lennert, K., Mohri, N., Stein, H., Kaiserling, E. and Muller-Hermelink, H.K. (1978)Malignant Lymphomas Other Than Hodgkin’s Disease. Berlin, Heidelberg, New York: Springer-Verlag.Google Scholar
  21. 21.
    Rappaport, H. (1966)Tumors Of The Hematopoietic System. Armed Forces Institute of Pathology. Washington. D.C.Google Scholar
  22. 22.
    Vandenberghe, E., De Wolf-Peeters, C., van den Oord, J., Wlodarska, I.D., J, Stul, M., Thomas, J., Michaux, J.L., Mecucci, C., Cassiman, J.J.et al. (1991) Translocation (11;14): a cytogenetic anomaly associated with B-cell lymphomas of non-follicle centre cell lineage.Journal of Pathology 163, 13–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Ince, C., Blick, M., Lee, M., Pathak, S., Vadhan-Raj, S., Selvanayagam, P.G., JU and Cabanillas, F. (1988) Bcl-1 gene rearrangements in B cell lymphoma.Leukemia 2, 343–6.PubMedGoogle Scholar
  24. 24.
    Koduru, P.R.K., Offit, K. and Filippa, D.A. (1989) Molecular analysis of breaks in BCL-1 proto-oncogene in B-cell lymphomas with abnormalities of 11q13.Oncogene 4, 929–34.PubMedGoogle Scholar
  25. 25.
    Jaffe, E.S., Bookman, M.A. and Longo, D.L. (1987) Lymphocytic lymphoma of intermediate differentiation-mantle zone lymphoma: A distinct subtype of B-cell lymphoma.Human Pathology 18, 877–80.PubMedCrossRefGoogle Scholar
  26. 26.
    Segal, G.H., Masih, A.S., Fox, A.C., Jorgensen, T., Scott, M. and Braylan, R.C. (1995) CD5-expressing B-cell non-Hodgkin’s lymphomas with bcl-1 gene rearrangement have a relatively homogeneous immunophenotype and are associated with an overall poor prognosis.Blood 85, 1570–9.PubMedGoogle Scholar
  27. 27.
    Athan, E., Foitl, D.R. and Knowles, D.M. (1991) bcl-1 rearrangement. Frequency and clinical significance among B-cell chronic lymphocytic leukemias and non-Hodgkin’s lymphomas.American Journal of Pathology 138, 591–9.PubMedGoogle Scholar
  28. 28.
    Gaidano, G., Newcomb, E.W., Gong, J.Z., Tassi, V., Neri, A., Cortelezzi, A.C., R, Baldini, L. and Dalla-Favera, R. (1994) Analysis of alterations of oncogenes and tumor suppressor genes in chronic lymphocytic leukemia.American Journal of Pathology 144, 1312–19.PubMedGoogle Scholar
  29. 29.
    Newman, R.A., Peterson, B., Davey, F.R., Brabyn, C., Collins, H., Brunetto, V.L.D., DB, Weiss, R.B., Royston, I., Millard, F.E.et al. (1993) Phenotypic markers and BCL-1 gene rearrangements in B-cell chronic lymphocytic leukemia: a Cancer and Leukemia Group B study.Blood 82, 1239–46.PubMedGoogle Scholar
  30. 30.
    Ott, M.M., Muller-Hermelink, H.K., Schmitt, B. and Feller, A.C. (1991) Chromosomal translocation detected by bcl-1 and bcl-2 rearrangement in low-grade B-cell lymphomas in a European population.Histopathology 19, 163–7.PubMedCrossRefGoogle Scholar
  31. 31.
    Pombo de Oliveira, M.S., Jaffe, E.S. and Catovsky, D. (1989) Leukaemic phase of mantle zone (intermediate) lymphoma: its characterisation in 11 cases.Journal of Clinical Pathology 42, 962–72.CrossRefGoogle Scholar
  32. 32.
    Williams, M.E., Meeker, T.C. and Swerdlow, S.H. (1991) Rearrangement of the chromosome 11 bcl-1 locus in centrocytic lymphoma: analysis with multiple breakpoint probes.Blood 78, 493–8.PubMedGoogle Scholar
  33. 33.
    Williams, M.E., Swerdlow, S.H., Rosenberg, C.L. and Arnold, A. (1992) Characterization of chromosome 11 translocation breakpoints at the bcl-1 and PRAD1 loci in centrocytic lymphoma.Cancer Research 52, 5541s-4s.PubMedGoogle Scholar
  34. 34.
    de Boer, C.J., Loyson, S., Kluin, P.M., Kluin-Nelemans, H.C., Schuuring, E. and vanKrieken J.H. (1993) Multiple breakpoints within the BCL-1 locus in B-cell lymphoma: rearrangements of the cyclin D1 gene.Cancer Research 53, 4148–52.PubMedGoogle Scholar
  35. 35.
    Ott, M.M., Ott, G., Kuse, R., Porowski, P., Gunzer, U. and Feller, A.C.M. (1994) The anaplastic variant of centrocytic lymphoma is marked by frequent rearrangements of the bcl-1 gene and high proliferation indices.Histopathology 24, 329–34.PubMedCrossRefGoogle Scholar
  36. 36.
    Williams, M.E., Swerdlow, S.H., Rosenberg, C.L. and Arnold, A. (1993) Chromosome 11 translocation break-points at the PRAD1/cyclin D1 gene locus in centrocytic lymphoma.Leukemia 7, 241–5.PubMedGoogle Scholar
  37. 37.
    Molot, R.J., Meeker, T.C., Wittwer, C.T., Perkins, S.L., Segal, G.H., Masih, A.S.B., RC and Kjeldsberg, C.R. (1994) Antigen expression and polymerase chain reaction amplification of mantle cell lymphomas.Blood 83, 1626–31.PubMedGoogle Scholar
  38. 38.
    Williams, M.E. and Swerdlow, S.H. (1994) Cyclin D1 over-expression in non-Hodgkin’s lymphoma with chromosome 11 bcl-1 rearrangement.Annals of Oncology 5 (Suppl 1), 71–3.PubMedGoogle Scholar
  39. 39.
    Yang, W.I., Zukerberg, L.R., Motokura, T., Arnold, A. and Harris, N.L. (1994) Cyclin D1 (Bcl-1, PRAD1) protein expression in low-grade B-cell lymphomas and reactive hyperplasia.American Journal of Pathology 145, 86–96.PubMedGoogle Scholar
  40. 40.
    Clark, H.M., Jones, D.B. and Wright, D.H. (1992) Cytogenetic and molecular studies of t(14;18) and t(14;19) in nodal and extranodal B-cell lymphoma.Journal of Pathology 166, 129–37.PubMedCrossRefGoogle Scholar
  41. 41.
    Tashiro, S., Takechi, M., Asou, H., Takauchi, K., Kyo, T., Dohy, H., Kikuchi, M.K. and Tsujimoto, Y. (1992) Cytogenetic 2; 18 and 18; 22 translocation in chronic lymphocytic leukemia with juxtaposition of bcl-2 and immunoglobulin light chain genes.Oncogene 7, 573–7.PubMedGoogle Scholar
  42. 42.
    Hillion, J., Mecucci, C., Aventin, A., Leroux, D., Wlodarska, I., Van DenBerghe, H. and Larsen, C.J. (1991) A variant translocation t(2;18) in follicular lymphoma involves the 5′ end of bcl-2 and Ig kappa light chain gene.Oncogene 6, 169–72.PubMedGoogle Scholar
  43. 43.
    Fiedler, W., Weh, H.J., Zeller, W., Fonatsch, C., Hillion, J., Larsen, C.W., B and Hossfeld, D.K. (1991) Translocation (14; 18) and (8; 22) in three patients with acute leukemia/lymphoma following centrocytic/centroblastic non-Hodgkin’s lymphoma.Annals of Hematology 63, 282–7.PubMedCrossRefGoogle Scholar
  44. 44.
    Zelenetz, A.D., Chu, G., Galili, N., Bangs, C.D., Horning, S.J., Donlon, T.A.C., ML and Levy, R. (1991) Enhanced detection of the t(14;18) translocation in malignant lymphoma using pulsed-field gel electrophoresis.Blood 78, 1552–60.PubMedGoogle Scholar
  45. 45.
    Matsuyama, F., Fukuhara, S., Oguma, S., Amakawa, R., Tanabe, S., Kato, I.H., T Yamabe, H., Abe, M., Wakasa, H.et al. (1992) Geographical aspects of bcl-2 gene involvement in Japanese patients with non-Hodgkin’s B-cell lymphomas.International Journal of Hematology 55, 71–9.PubMedGoogle Scholar
  46. 46.
    Seto, M., Yamamoto, K., Osada, H. and Ueda, R. (1991) [BCL-2 gene in lymphocytic malignancy]. [Review] [Japanese].Gan to Kagaku Ryoho 18, 1106–11.PubMedGoogle Scholar
  47. 47.
    Chen, P.M., Lin, S.H., Seto, M., Chao, S.C., Chiou, T.J., Hsieh, R.K., Lin, C.Z., Fan, S., Tzeng, C.H., Ueda, R.et al. (1993) Rearrangement of bcl-2 genes in malignant lymphomas in Chinese patients.Cancer 72, 3701–6.PubMedCrossRefGoogle Scholar
  48. 48.
    Seto, M., Osada, H., Ueda, R., Ito, C., Iwaki, O., Oyama, A. and Suchi, T.T. (1991) bcl-2 translocation in Japanese B cell lymphoma: novel bcl-2 translocation with immunoglobulin heavy chain diversity segment.Japanese Journal of Cancer Research 82, 65–71.PubMedGoogle Scholar
  49. 49.
    Takechi, M., Tanaka, K., Hashimoto, T., Asaoku, H., Dohy, H. and Kikuchi, M.K., (1991) Cytogenetic, molecular biological and clinical study of B-cell lymphomas with 14;18 translocation in Japanese patients.Leukemia 5, 1069–75.PubMedGoogle Scholar
  50. 50.
    Abe, M., Ono, N., Tominaga, K., Hojo, H., Seto, M., Fukuhara, S. and Wakasa, H. (1992) Histogenesis of diffuse small cleaved cell lymphoma. An immunohistochemical and molecular genetic (bcl-2 gene) study with comparison to follicular small cleaved cell lymphoma and mantle zone lymphoma.Cancer 70, 821–9.PubMedCrossRefGoogle Scholar
  51. 51.
    Leith, C.P., Willman, C.L., Spier, C.M., Miller, T.P. and Grogan, T.M. (1994) The presence of bcl-1 and bcl-2 gene rearrangements in diffuse small cleaved-cell lymphoma. A disease with diverse molecular and immunophenotypic findings.Diagnostic Molecular Pathology 3, 178–83.PubMedCrossRefGoogle Scholar
  52. 52.
    Cotter, F.E., Price, C., Meerabux, J., Zucca, E. and Young, B.D. (1991) Direct sequence analysis of 14q+ and 18q- chromosome junctions at the MBR and MCR revealing clustering within the MBR in follicular lymphoma.Annals of Oncology 2 (Suppl 2), 93–7.PubMedGoogle Scholar
  53. 53.
    Kneba, M., Eick, S., Herbst, H., Willigeroth, S., Pott, C., Bolz, I., Bergholz, M., Neumann, C., Stein, H. and Krieger, G. (1991) Frequency and structure of t(14;18) major breakpoint regions in non-Hodgkin’s lymphomas typed according to the Kiel classification: analysis by direct DNA sequencing.Cancer Research 51, 3243–50.PubMedGoogle Scholar
  54. 54.
    Liu, J., Johnson, R.M. and Traweek, S.T. (1993) Rearrangement of the BCL-2 gene in follicular lymphoma. Detection by PCR in both fresh and fixed tissue samples,Diagnostic Molecular Pathology 2, 241–7.PubMedGoogle Scholar
  55. 55.
    Chen, Y.T., Whitney, K.D. and Chen, Y. (1994) Clonality analysis of B-cell lymphoma in fresh-frozen and paraffinembedded tissues: the effects of variable polymerase chain reaction parameters.Modern Pathology 7, 429–34.PubMedGoogle Scholar
  56. 56.
    Mitani, S., Aoki, N., Mizutani, S., Fujiwara, M., Kitagawa, T., Uehara, T. and Mori, S. (1993) bcl-2 gene rearrangement analysis of Japanese follicular lymphomas by polymerase chain reaction in formalin-fixed, paraffin-embedded tissue specimens.Japanese Journal of Cancer Research 84, 37–41.PubMedGoogle Scholar
  57. 57.
    Aster, J.C., Kobayashi, Y., Shiota, M., Mori, S. and Sklar, J. (1992) Detection of the t(14;18) at similar frequencies in hyperplastic lymphoid tissues from American and Japanese patients.American Journal of Pathology 141, 291–9.PubMedGoogle Scholar
  58. 58.
    Limpens, J., de Jong, D., van Krieken, J.H., Price, C.G., Young, B.D., van Ommen, G.J. and Kluin, P.M. (1991) Bcl-2/JH rearrangements in benign lymphoid tissues with follicular hyperplasia.Oncogene 6, 2271–6.PubMedGoogle Scholar
  59. 59.
    Kube, M.J., McDonald, D.A., Quin, J.W. and Greenberg, M.L. (1994) Use of archival and fresh cytologic material for the polymerase chain reaction. Detection of the bcl-2 oncogene in lymphoid tissue obtained by fine needle biopsy.Analytical and Quantitative Cytology and Histology 16, 174–82.PubMedGoogle Scholar
  60. 60.
    Corbally, N., Grogan, L., Dervan, P.A. and Carney, D.N. (1992) The detection of specific gene rearrangements in non-Hodgkin’s lymphoma using the polymerase chain reaction.British Journal of Cancer 66, 805–9.PubMedGoogle Scholar
  61. 61.
    Berinstein, N.L., Jamal, H.H., Kuzniar, B., Klock, R.J. and Reis, M.D. (1993) Sensitive and reproducible detection of occult disease in patients with follicular lymphoma by PCR amplification of t(14;18) both pre- and post-treatment.Leukemia 7, 113–9.PubMedGoogle Scholar
  62. 62.
    Hickish, T.F., Purvies, H., Mansi, J., Soukop, M. and Cunningham, D. (1991) Molecular monitoring of low grade non-Hodgkin’s lymphoma by gene amplification.British Journal of Cancer 64, 1161–3.PubMedGoogle Scholar
  63. 63.
    Yuan, R., Dowling, P., Zucca, E., Diggelmann, H. and Cavalli, F. (1993) Detection of bcl-2/JH rearrangement in follicular and diffuse lymphoma: concordant results of peripheral blood and bone marrow analysis at diagnosis.British Journal of Cancer 67, 922–5.PubMedGoogle Scholar
  64. 64.
    Negrin, R.S. and Pesando, J. (1994) Detection of tumor cells in purged bone marrow and peripheral-blood mononuclear cells by polymerase chain reaction amplification of bcl-2 translocations.Journal of Clinical Oncology 12, 1021–27.PubMedGoogle Scholar
  65. 65.
    McLaughlin, P., Hagemeister, F.B., Swan, F., Cabanillas, F., Romaguera, J.R., Lee, M.S., Pate, O., Sarris, A. and Younes, A. (1994) Intensive conventional-dose chemotherapy for stage IV low-grade lymphoma: high remission rates and reversion to negative of peripheral blood bcl-2 rearrangement.Annals of Oncology 5 (Suppl 2), 73–7.PubMedGoogle Scholar
  66. 66.
    Gribben, J.G., Saporito, L., Barber, M., Blake, K.W., Edwards, R.M., Griffin, J.D.F., AS and Nadler, L.M. (1992) Bone marrows of non-Hodgkin’s lymphoma patients with a bcl-2 translocation can be purged of polymerase chain reaction-detectable lymphoma cells using monoclonal antibodies and immunomagnetic bead depletion.Blood 80, 1083–89.PubMedGoogle Scholar
  67. 67.
    Hardingham, J.E., Kotasek, D., Sage, R.E., Dobrovic, A., Gooley, T. and Dale, B.M. (1993) Molecular detection of residual lymphoma cells in peripheral blood stem cell harvests and following autologous transplantation.Bone Marrow Transplantation 11, 15–20.PubMedGoogle Scholar
  68. 68.
    Gribben, J.G., Neuberg, D., Freedman, A.S., Gimmi, C.D., Pesek, K.W., Barber, M.S., L, Woo, S.D., Coral, F., Spector, N.et al. (1993) Detection by polymerase chain reaction of residual cells with the bcl-2 translocation is associated with increased risk of relapse after autologous bone marrow transplantation for B-cell lymphoma.Blood 81, 3449–57.PubMedGoogle Scholar
  69. 69.
    Haas, R., Moos, M., Karcher, A., Mohle, R., Witt, B., Goldschmidt, H., Fruhauf, S., Flentje, M., Wannenmacher, M. and Hunstein, W. (1994) Sequential high-dose therapy with peripheral-blood progenitor-cell support in low-grade non-Hodgkin’s lymphoma.Journal of Clinical Oncology 12, 1685–92.PubMedGoogle Scholar
  70. 70.
    Soubeyran, P., Cabanillas, F. and Lee, M.S. (1993) Analysis of the expression of the hybrid gene bcl-2/IgH in follicular lymphomas.Blood 81, 122–7.PubMedGoogle Scholar
  71. 71.
    Pisa, E.K., Pisa, P., Kang, H.I. and Fox, R.I. (1991) High frequency of t(14;18) translocation in salivary gland lymphomas from Sjogren’s syndrome patients.Journal of Experimental Medicine 174, 1245–50.PubMedCrossRefGoogle Scholar
  72. 72.
    Sugai, S., Saito, I., Masaki, Y., Takeshita, S., Shimizu, S. and Tachibana, J.M., (1994) Rearrangement of the rheumatoid factor-related germline gene Vg and bcl-2 expression in lymphoproliferative disorders in patients with Sjogren’s syndrome.Clinical Immunology and Immunopathology 72, 181–6.PubMedCrossRefGoogle Scholar
  73. 73.
    Chang, K.L., Arber, D.A., Shibata, D., Rappaport, H. and Weiss, L.M. (1994) Follicular small lymphocytic lymphoma.American Journal of Surgical Pathology 18, 999–1009.PubMedCrossRefGoogle Scholar
  74. 74.
    Isaacson, P.G., Wotherspoon, A.C., Diss, T. and Pan, L.X. (1991) Follicular colonization in B-cell tissue.American Journal of Surgical Pathology 15, 819–28.PubMedGoogle Scholar
  75. 75.
    Straka, C., Mielke, B., Eichelmann, A., Trede, I., Ho, A.D. and Moller, P. (1993) Bcl-2 gene rearrangements in primary B-cell lymphoma of the gastrointestinal tract reveal follicular lymphoma as a subtype.Leukemia 7, 268–73.PubMedGoogle Scholar
  76. 76.
    Shepherd, N.A., McCarthy, K.P. and Hall, P.A. (1991) 14;18 translocation in primary intestinal lymphoma: detection by polymerase chain reaction in routinely processed tissue.Histopathology 18, 415–9.PubMedCrossRefGoogle Scholar
  77. 77.
    Monaghan, P., Robertson, D., Amos, T.A., Dyer, M.J., Mason, D.Y. and Greaves, M.F. (1992) Ultrastructural localization of bcl-2 protein.Journal of Histochemistry and Cytochemistry 40, 1819–25.PubMedGoogle Scholar
  78. 78.
    Krajewski, S., Tanaka, S., Takayama, S., Schibler, M.J., Fenton, W. and Reed, J.C. (1993) Investigation of the subcellular distribution of the bcl-2 oncoprotein: residence in the nuclear envelope, endoplasmic reticulum, and outer mitochondrial membranes.Cancer Research 53, 4701–14.PubMedGoogle Scholar
  79. 79.
    Ngan, B.-Y., Chen-Levy, Z., Weiss, L.M., Warnke, R.A. and Cleary, M.L. (1988) Expression in non-Hodgkin’s lymphoma of the bcl-2 protein associated with the t(14;18) chromosomal translocation.New England Journal of Medicine 318, 1638–44.PubMedGoogle Scholar
  80. 80.
    Chleq-Deschamps, C.M., LeBrun, D.P., Huie, P., Besnier, D.P., Warnke, R.A., Sibley, R.K. and Cleary, M.L. (1993) Topographical dissociation of BCL-2 messenger RNA and protein expression in human lymphoid tissues.Blood 81, 293–8.PubMedGoogle Scholar
  81. 81.
    Zutter, M., Hockenbery, D., Silverman, G.A. and Korsmeyer, S.J. (1991) Immunolocalization of the Bcl-2 protein within hematopoietic neoplasms.Blood 78, 1062–8.PubMedGoogle Scholar
  82. 82.
    Mariano, M.T., Moretti, L., Donelli, A., Grantini, M., Montagnani, G., Di Prisco, A., Torelli, G., Torelli, U. and Narni, F. (1992) bcl-2 gene expression in hematopoietic cell differentiation.Blood 80, 768–75.PubMedGoogle Scholar
  83. 83.
    Cerroni, L., Volkenandt, M., Rieger, E., Soyer, H.P. and Kerl, H. (1994) bcl-2 protein expression and correlation with the interchromosomal 14; 18 translocation in cutaneous lymphomas and pseudolymphomas.Journal of Investigative Dermatology 102, 231–5.PubMedCrossRefGoogle Scholar
  84. 84.
    Pettersson, M., Jernberg-Wiklund, H., Larsson, L.G., Sundstrom, C., Givol, I.T., Y and Nilsson, K. (1992) Expression of the bcl-2 gene in human multiple myeloma cell lines and normal plasma cells.Blood 79, 495–502.PubMedGoogle Scholar
  85. 85.
    Gaulard, P., d’Agay, M.F., Peuchmaur, M., Brousse, N., Gisselbrecht, C.S., P, Diebold, J. and Mason, D.Y. (1992) Expression of the bcl-2 gene product in follicular lymphoma.American Journal of Pathology 140, 1089–95.PubMedGoogle Scholar
  86. 86.
    Reed, J.C., Tanaka, S. and Cuddy, M. (1992) Cell cycle analysis of p26-BCL-2 protein levels in proliferating lymphoma and leukemia cell lines.Cancer Research 52, 2802–5.PubMedGoogle Scholar
  87. 87.
    Henderson, S., Rowe, M., Gregory, C., Croom-Carter, D., Wang, F., Longnecker, R., Kieff, E. and Rickinson, A. (1991) Induction of bcl-2 expression by Epstein-Barr virus latent membrane protein 1 protects infected B cells from programmed cell death.Cell 65, 1107–15.PubMedCrossRefGoogle Scholar
  88. 88.
    Seite, P., Hillion, J., d’Agay, M.F., Gaulard, P., Cazals, D., Badoux, F., Berger, R. and Larsen, C.J. (1993) BCL2 gene activation and protein expression in follicular lymphoma: a report on 64 cases.Leukemia 7, 410–7.PubMedGoogle Scholar
  89. 89.
    Liu, Y.J., Mason, D.Y., Johnson, G.D., Abbot, S., Gregory, C.D., Hardie, D.L., Gordon, J. and MacLennan, I.C. (1991) Germinal center cells express bcl-2 protein after activation by signals which prevent their entry into apoptosis.European Journal of Immunology 21, 1905–10.PubMedCrossRefGoogle Scholar
  90. 90.
    Schmid, C. and Isaacson, P.G. (1994) Proliferation centres in B-cell malignant lymphoma lymphocytic (B-CLL): an immunophenotypic study.Histopathology 24, 445–51.PubMedCrossRefGoogle Scholar
  91. 91.
    Reed, J.C., Miyashita, T., Cuddy, M. and Cho, D. (1992) Regulation of p26-bcl-2 protein levels in human peripheral blood lymphocytes.Laboratory Investigation 67, 443–9.PubMedGoogle Scholar
  92. 92.
    Swerdlow, S.H., Utz, G.L. and Williams, M.E. (1993) Bcl-2 protein in centrocytic lymphoma; a paraffin section study.Leukemia 7, 1456–8.PubMedGoogle Scholar
  93. 93.
    Schena, M., Gottardi, D., Ghia, P., Larsson, L.G., Carlsson, M. and Nilsson, K.C. (1993) The role of Bcl-2 in the pathogenesis of B chronic lymphocytic leukemia. [Review],Leukemia and Lymphoma 11, 173–9.PubMedCrossRefGoogle Scholar
  94. 94.
    Ben-Ezra, J.M., King, B.E., Harris, A.C., Todd, W.M. and Kornstein, M.J. (1994) Staining for Bcl-2 protein helps to distinguish benign from malignant lymphoid aggregates in bone marrow biopsies.Modern Pathology 7, 560–4.PubMedGoogle Scholar
  95. 95.
    Wang, J., Raffeld, M., Medeiros, L.J., Longo, D.L., Jaffe, E.S. and Duffey, P.S. (1993) Follicular center cell lymphoma with the t(14;18) translocation in which the rearranged BCL-2 gene is silent.Leukemia 7, 1834–9.PubMedGoogle Scholar
  96. 96.
    McDonnell, T.J., Marin, M.C., Hsu, B., Brisbay, S.M., McConnell, K., Tu, S.M.C., ML and Rodriguez-Villanueva, J. (1993) The bcl-2 oncogene: apoptosis and neoplasia. [Review].Radiation Research 136, 307–12.PubMedCrossRefGoogle Scholar
  97. 97.
    Amakawa, R., Fukuhara, S., Ohno, H., Matsuyama, F., Kato, I., Tanabe, S.S.P., Mizuta, T.R., Honjo, T. and Okuma, M. (1991) Genomic organization of IgH gene compared with the expression of Bcl-2 gene in t(14;18)-positive lymphoma.Blood 77, 1970–6.PubMedGoogle Scholar
  98. 98.
    Vuist, W.M., Levy, R. and Maloney, D.G. (1994) Lymphoma regression induced by monoclonal anti-idiotypic antibodies correlates with their ability to induce Ig signal transduction and is not prevented by tumor expression of high levels of bcl-2 protein.Blood 83, 899–906.PubMedGoogle Scholar
  99. 99.
    Bonnefoy-Berard, N., Genestier, L., Flacher, M., Rouault, J.P., Lizard, G.M.M. and Revillard, J.P. (1994) Apoptosis induced by polyclonal antilymphocyte globulins in human B-cell lines.Blood 83, 1051–9.PubMedGoogle Scholar
  100. 100.
    Pezzella, F., Jones, M., Ralfkiaer, E., Ersboll, J., Gatter, K.C. and Mason, D.Y. (1992) Evaluation of bcl-2 protein expression and 14;18 translocation as prognostic markers in follicular lymphoma.British Journal of Cancer 65, 87–9.PubMedGoogle Scholar
  101. 101.
    Dalla-Favera, R., Ye, B.H., Lo Coco, F., Gaidano, G., Lista, F., Knowles, D.M.L., DC, Offit, K. and Chaganti, R.S. (1994) Identification of genetic lesions associated with diffuse large-cell lymphoma. [Review].Annals of Oncology 5 (Suppl 1) 55–60.PubMedGoogle Scholar

Copyright information

© Humana Press Inc. 1995

Authors and Affiliations

  • Howard Ratech
    • 1
  1. 1.Department of PathologyAlbert Einstein College of Medicine/Montefiore Medical CenterBronxUSA

Personalised recommendations