1. Assessment of CD37 B-cell antigen and cell of origin significantly improves risk prediction in diffuse large B-cell lymphoma
- Author
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Eric D. Hsi, Charlotte M. de Winde, Maurilio Ponzoni, Jane N. Winter, Miguel A. Piris, Carlo Visco, Jing Wang, Michiel van den Brand, John C. Byrd, Youli Zu, Ben M. Parsons, William W.L. Choi, Alexandar Tzankov, L. Jeffrey Medeiros, Govind Bhagat, Ken H. Young, Karen Dybkær, J. Han van Krieken, Frederick B. Hagemeister, Ling Li, Zijun Y. Xu-Monette, Yong Li, Kristy L. Richards, Kausar J. Jabbar, Jooryung Huh, Attilio Orazi, Annemiek B. van Spriel, Andrés J.M. Ferreri, Ganiraju C. Manyam, April Chiu, Michael Boe Møller, Michael Wang, Xu-Monette, Z. Y., Li, L., Byrd, J. C., Jabbar, K. J., Manyam, G. C., De Winde, C. M., Van Den Brand, M., Tzankov, A., Visco, C., Wang, J., Dybkaer, K., Chiu, A., Orazi, A., Zu, Y., Bhagat, G., Richards, K. L., Hsi, E. D., Choi, W. W. L., Huh, J., Ponzoni, M., Ferreri, A. J. M., Moller, M. B., Parsons, B. M., Winter, J. N., Wang, M., Hagemeister, F. B., Piris, M. A., Van Krieken, J. H., Medeiros, L. J., Li, Y., Van Spriel, A. B., and Young, K. H.
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0301 basic medicine ,Male ,Lymphoma ,Tetraspanins ,Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] ,Antigens, CD20 ,Antigens, Neoplasm ,Antineoplastic Combined Chemotherapy Protocols ,B-Lymphocytes ,Female ,Gene Expression Profiling ,Gene Expression Regulation, Neoplastic ,Germinal Center ,Humans ,Lymphoma, Large B-Cell, Diffuse ,Middle Aged ,Models, Biological ,Multivariate Analysis ,Mutation ,NF-kappa B ,Prognosis ,Programmed Cell Death 1 Receptor ,Protein Transport ,Proto-Oncogene Proteins c-myc ,RNA, Messenger ,Risk Factors ,Survival Analysis ,Treatment Outcome ,Tumor Suppressor Protein p53 ,Messenger ,CHOP ,Biochemistry ,International Prognostic Index ,Models ,immune system diseases ,hemic and lymphatic diseases ,CD20 ,Lymphoid Neoplasia ,Hematology ,BCL6 ,Diffuse ,Rituximab ,medicine.drug ,Immunology ,Biology ,03 medical and health sciences ,medicine ,Large B-Cell ,Antigens ,Neoplastic ,Staining and Labeling ,Germinal center ,Cell Biology ,medicine.disease ,Biological ,030104 developmental biology ,Gene Expression Regulation ,Cancer research ,biology.protein ,Neoplasm ,RNA ,Diffuse large B-cell lymphoma - Abstract
Contains fulltext : 171804.pdf (Publisher’s version ) (Closed access) CD37 (tetraspanin TSPAN26) is a B-cell surface antigen widely expressed on mature B cells. CD37 is involved in immune regulation and tumor suppression but its function has not been fully elucidated. We assessed CD37 expression in de novo diffuse large B-cell lymphoma (DLBCL), and investigated its clinical and biologic significance in 773 patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and 231 patients treated with CHOP. We found that CD37 loss (CD37-) in approximately 60% of DLBCL patients showed significantly decreased survival after R-CHOP treatment, independent of the International Prognostic Index (IPI), germinal center B-cell-like (GCB)/activated B-cell-like (ABC) cell of origin, nodal/extranodal primary origin, and the prognostic factors associated with CD37-, including TP53 mutation, NF-kappaBhigh, Mychigh, phosphorylated STAT3high, survivinhigh, p63-, and BCL6 translocation. CD37 positivity predicted superior survival, abolishing the prognostic impact of high IPI and above biomarkers in GCB-DLBCL but not in ABC-DLBCL. Combining risk scores for CD37- status and ABC cell of origin with the IPI, defined as molecularly adjusted IPI for R-CHOP (M-IPI-R), or IPI plus immunohistochemistry (IHC; IPI+IHC) for CD37, Myc, and Bcl-2, significantly improved risk prediction over IPI alone. Gene expression profiling suggested that decreased CD20 and increased PD-1 levels in CD37- DLBCL, ICOSLG upregulation in CD37+ GCB-DLBCL, and CD37 functions during R-CHOP treatment underlie the pivotal role of CD37 status in clinical outcomes. In conclusion, CD37 is a critical determinant of R-CHOP outcome in DLBCL especially in GCB-DLBCL, representing its importance for optimal rituximab action and sustained immune responses. The combined molecular and clinical prognostic indices, M-IPI-R and IPI+IHC, have remarkable predictive values in R-CHOP-treated DLBCL.
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- 2016
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