FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 320:1047-1054 April 20, 1989 Number 16 Next

	Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

Abstract

Approximately half the patients with diffuse or follicular large-cell or mixed large- and small-cell lymphoma enter a prolonged remission or are cured after receiving combined-drug therapy. It has been unclear, however, why the other half do not respond. We evaluated 54 previously untreated patients with diffuse lymphoma and 20 with follicular lymphoma, all of whom had a large-cell component and Stage II through IV disease, subsequently treated with combined chemotherapy. Different recurrent genomic defects were associated with differences in the response to treatment. Among the 54 patients with diffuse lymphoma, all 12 patients with a duplication of chromosome 3p had a complete clinical remission after a median follow-up of 39 months (11 patients survived). In contrast, all seven patients with a duplication of chromosome 2p had a partial response or no response to treatment and a median survival of six months (all died). Among the 20 patients with follicular lymphoma, all 5 patients with duplication 3p or +3 had a complete clinical remission (all survived), and 3 of 4 patients with duplication 2p or +2 had no response or a partial response to treatment and died. Twenty-three patients with B-cell non-immunoblastic lymphoma or follicular lymphoma who had a bcl-2 oncogene rearrangement had a poorer response to therapy (7 of 23 with complete remission) than the patients without bcl-2 rearrangement (21 of 26 with complete remission). We conclude that in large-cell or mixed-cell lymphoma, duplication of chromosome 3p is associated with a relatively good prognosis and duplication of chromosome 2p or bcl-2 oncogene rearrangement is associated with a relatively poor prognosis. Because such multiple recurrent genomic defects are also common in most other types of cancer, they may have general prognostic importance.

Source Information

Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis 55455.

This article has been cited by other articles:

• Ennishi, D., Takeuchi, K., Yokoyama, M., Asai, H., Mishima, Y., Terui, Y., Takahashi, S., Komatsu, H., Ikeda, K., Yamaguchi, M., Suzuki, R., Tanimoto, M., Hatake, K. (2008). CD5 expression is potentially predictive of poor outcome among biomarkers in patients with diffuse large B-cell lymphoma receiving rituximab plus CHOP therapy. Ann Oncol 0: mdn392v1-mdn392 [Abstract] [Full Text]  
• Reed, J. C. (2008). Bcl-2-family proteins and hematologic malignancies: history and future prospects. Blood 111: 3322-3330 [Abstract] [Full Text]  
• Kelly, P. N., Puthalakath, H., Adams, J. M., Strasser, A. (2007). Endogenous bcl-2 is not required for the development of E{micro}-myc induced B-cell lymphoma. Blood 109: 4907-4913 [Abstract] [Full Text]  
• Wallace, D. J., Shen, D., Reed, G. F., Miyanaga, M., Mochizuki, M., Sen, H. N., Dahr, S. S., Buggage, R. R., Nussenblatt, R. B., Chan, C.-C. (2006). Detection of the bcl-2 t(14;18) Translocation and Proto-Oncogene Expression in Primary Intraocular Lymphoma.. IOVS 47: 2750-2756 [Abstract] [Full Text]  
• Bea, S., Zettl, A., Wright, G., Salaverria, I., Jehn, P., Moreno, V., Burek, C., Ott, G., Puig, X., Yang, L., Lopez-Guillermo, A., Chan, W. C., Greiner, T. C., Weisenburger, D. D., Armitage, J. O., Gascoyne, R. D., Connors, J. M., Grogan, T. M., Braziel, R., Fisher, R. I., Smeland, E. B., Kvaloy, S., Holte, H., Delabie, J., Simon, R., Powell, J., Wilson, W. H., Jaffe, E. S., Montserrat, E., Muller-Hermelink, H.-K., Staudt, L. M., Campo, E., Rosenwald, A., for the Lymphoma/Leukemia Molecular Profiling Proj, (2005). Diffuse large B-cell lymphoma subgroups have distinct genetic profiles that influence tumor biology and improve gene-expression-based survival prediction. Blood 106: 3183-3190 [Abstract] [Full Text]  
• De Paepe, P., Achten, R., Verhoef, G., Wlodarska, I., Stul, M., Vanhentenrijk, V., Praet, M., De Wolf-Peeters, C. (2005). Large Cleaved and Immunoblastic Lymphoma May Represent Two Distinct Clinicopathologic Entities Within the Group of Diffuse Large B-Cell Lymphomas. JCO 23: 7060-7068 [Abstract] [Full Text]  
• Abramson, J. S., Shipp, M. A. (2005). Advances in the biology and therapy of diffuse large B-cell lymphoma: moving toward a molecularly targeted approach. Blood 106: 1164-1174 [Abstract] [Full Text]  
• Nencioni, A., Wille, L., Dal Bello, G., Boy, D., Cirmena, G., Wesselborg, S., Belka, C., Brossart, P., Patrone, F., Ballestrero, A. (2005). Cooperative Cytotoxicity of Proteasome Inhibitors and Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand in Chemoresistant Bcl-2-Overexpressing Cells. Clin. Cancer Res. 11: 4259-4265 [Abstract] [Full Text]  
• Bea, S., Colomo, L., Lopez-Guillermo, A., Salaverria, I., Puig, X., Pinyol, M., Rives, S., Montserrat, E., Campo, E. (2004). Clinicopathologic Significance and Prognostic Value of Chromosomal Imbalances in Diffuse Large B-Cell Lymphomas. JCO 22: 3498-3506 [Abstract] [Full Text]  
• Ballestrero, A., Nencioni, A., Boy, D., Rocco, I., Garuti, A., Mela, G. S., Van Parijs, L., Brossart, P., Wesselborg, S., Patrone, F. (2004). Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Cooperates with Anticancer Drugs to Overcome Chemoresistance in Antiapoptotic Bcl-2 Family Members Expressing Jurkat Cells. Clin. Cancer Res. 10: 1463-1470 [Abstract] [Full Text]  
• Hans, C. P., Weisenburger, D. D., Greiner, T. C., Gascoyne, R. D., Delabie, J., Ott, G., Muller-Hermelink, H. K., Campo, E., Braziel, R. M., Jaffe, E. S., Pan, Z., Farinha, P., Smith, L. M., Falini, B., Banham, A. H., Rosenwald, A., Staudt, L. M., Connors, J. M., Armitage, J. O., Chan, W. C. (2004). Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood 103: 275-282 [Abstract] [Full Text]  
• Barrans, S. L., Evans, P. A. S., O'Connor, S. J. M., Kendall, S. J., Owen, R. G., Haynes, A. P., Morgan, G. J., Jack, A. S. (2003). The t(14;18) Is Associated with Germinal Center-derived Diffuse Large B-Cell Lymphoma and Is a Strong Predictor of Outcome. Clin. Cancer Res. 9: 2133-2139 [Abstract] [Full Text]  
• Biagi, J. J., Seymour, J. F. (2002). Insights into the molecular pathogenesis of follicular lymphoma arising from analysis of geographic variation. Blood 99: 4265-4275 [Abstract] [Full Text]  
• Nanjangud, G., Rao, P. H., Hegde, A., Teruya-Feldstein, J., Donnelly, G., Qin, J., Jhanwar, S. C., Zelenetz, A. D., Chaganti, R. S. K. (2002). Spectral karyotyping identifies new rearrangements, translocations, and clinical associations in diffuse large B-cell lymphoma. Blood 99: 2554-2561 [Abstract] [Full Text]  
• Aster, J. C., Longtine, J. A. (2002). Detection of BCL2 Rearrangements in Follicular Lymphoma. Am. J. Pathol. 160: 759-763 [Abstract] [Full Text]  
• Braziel, R. M., Arber, D. A., Slovak, M. L., Gulley, M. L., Spier, C., Kjeldsberg, C., Unger, J., Miller, T. P., Tubbs, R., Leith, C., Fisher, R. I., Grogan, T. M. (2001). The Burkitt-like lymphomas: a Southwest Oncology Group study delineating phenotypic, genotypic, and clinical features. Blood 97: 3713-3720 [Abstract] [Full Text]  
• Harris, N. L., Stein, H., Coupland, S. E., Hummel, M., Favera, R. D., Pasqualucci, L., Chan, W. C. (2001). New Approaches to Lymphoma Diagnosis. ASH Education Book 2001: 194-220 [Abstract] [Full Text]  
• Arber, D. A. (2000). Molecular Diagnostic Approach to Non-Hodgkin's Lymphoma. J. Mol. Diagn. 2: 178-190 [Full Text]  
• Akasaka, T., Akasaka, H., Ueda, C., Yonetani, N., Maesako, Y., Shimizu, A., Yamabe, H., Fukuhara, S., Uchiyama, T., Ohno, H. (2000). Molecular and Clinical Features of Non-Burkitt’s, Diffuse Large-Cell Lymphoma of B-Cell Type Associated With the c-MYC/Immunoglobulin Heavy-Chain Fusion Gene. JCO 18: 510-510 [Abstract] [Full Text]  
• Apostolidis, J., Gupta, R. K., Grenzelias, D., Johnson, P. W. M., Pappa, V. I., Summers, K. E., Salam, A., Adams, K., Norton, A. J., Amess, J. A. L., Matthews, J., Bradburn, M., Lister, T. A., Rohatiner, A. Z. S. (2000). High-Dose Therapy With Autologous Bone Marrow Support as Consolidation of Remission in Follicular Lymphoma: Long-Term Clinical and Molecular Follow-Up. JCO 18: 527-527 [Abstract] [Full Text]  
• Buggage, R. R., Velez, G., Myers-Powell, B., Shen, D., Whitcup, S. M., Chan, C.-C. (1999). Primary Intraocular Lymphoma With a Low Interleukin 10 to Interleukin 6 Ratio and Heterogeneous IgH Gene Rearrangement. Arch Ophthalmol 117: 1239-1242 [Abstract] [Full Text]  
• Lopez-Guillermo, A., Cabanillas, F., McDonnell, T. I., McLaughlin, P., Smith, T., Pugh, W., Hagemeister, F., Rodriguez, M. A., Romaguera, J. E., Younes, A., Sarris, A. H., Preti, H. A., Lee, M.-S. (1999). Correlation of Bcl-2 Rearrangement With Clinical Characteristics and Outcome in Indolent Follicular Lymphoma. Blood 93: 3081-3087 [Abstract] [Full Text]  
• Kramer, M.H.H., Hermans, J., Wijburg, E., Philippo, K., Geelen, E., van Krieken, J.H.J.M., de Jong, D., Maartense, E., Schuuring, E., Kluin, P.M. (1998). Clinical Relevance of BCL2, BCL6, and MYC Rearrangements in Diffuse Large B-Cell Lymphoma. Blood 92: 3152-3162 [Abstract] [Full Text]  
• Friess, H, Lu, Z, Graber, H U, Zimmermann, A, Adler, G, Korc, M, Schmid, R M, Buchler, M W (1998). bax, but not bcl-2, influences the prognosis of human pancreatic cancer. Gut 43: 414-421 [Abstract] [Full Text]  
• Winter, J. N., Andersen, J., Reed, J. C., Krajewski, S., Variakojis, D., Bauer, K. D., Fisher, R. I., Gordon, L. I., Oken, M. M., Jiang, S., Jeffries, D., Domer, P. (1998). BCL-2 Expression Correlates With Lower Proliferative Activity in the Intermediate- and High-Grade Non-Hodgkin's Lymphomas: An Eastern Cooperative Oncology Group and Southwest Oncology Group Cooperative Laboratory Study. Blood 91: 1391-1398 [Abstract] [Full Text]  
• Gascoyne, R. D., Adomat, S. A., Krajewski, S., Krajewska, M., Horsman, D. E., Tolcher, A. W., O'Reilly, S. E., Hoskins, P., Coldman, A. J., Reed, J. C., Connors, J. M. (1997). Prognostic Significance of Bcl-2 Protein Expression and Bcl-2 Gene Rearrangement in Diffuse Aggressive Non-Hodgkin's Lymphoma. Blood 90: 244-251 [Abstract] [Full Text]  
• Hanada, M., Aimé-Sempé, C., Sato, T., Reed, J. C. (1995). Structure-Function Analysis of Bcl-2 Protein. J. Biol. Chem. 270: 11962-11969 [Abstract] [Full Text]  
• Ritter, J. H., Wick, M. R. (1994). Posttransplant Lymphoproliferative Disorders: Immunohistologic Differential Diagnosis With Severe Allograft Rejection. INT J SURG PATHOL 2: 105-115 [Abstract]  
• Offit, K., Coco, F. L., Louie, D. C., Parsa, N. Z., Leung, D., Portlock, C., Ye, B. H., Lista, F., Filippa, D. A., Rosenbaum, A., Ladanyi, M., Jhanwar, S., Dalla-Favera, R., Chaganti, R.S.K. (1994). Rearrangement of the bcl-6 Gene as a Prognostic Marker in Diffuse Large-Cell Lymphoma. NEJM 331: 74-80 [Abstract] [Full Text]  
• Kluin, P. M. (1994). bcl-6 in Lymphoma -- Sorting Out a Wastebasket?. NEJM 331: 116-118 [Full Text]  
• The International Non-Hodgkin's Lymphoma Prognosti, (1993). A Predictive Model for Aggressive Non-Hodgkin's Lymphoma. NEJM 329: 987-994 [Abstract] [Full Text]