1. Loss of PRDM1/BLIMP-1 function contributes to poor prognosis of activated B-cell-like diffuse large B-cell lymphoma
- Author
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Nathan Fowler, M. Ponzoni, William W.L. Choi, Shuxing Zhang, Laura Pasqualucci, Ben M. Parsons, Ken H. Young, L. J. Medeiros, C. Visco, Youli Zu, Chi Young Ok, Xin Li, Zijun Y. Xu-Monette, Jooryung Huh, Jason R. Westin, Anna Ferreri, Govind Bhagat, Roberto N. Miranda, Alexander Tzankov, Vundavalli V. Murty, Jane N. Winter, M A Piris, Karen Dybkær, J.H.J.M. van Krieken, Ganiraju C. Manyam, Y Li, April Chiu, Michael Boe Møller, Kristy L. Richards, Jianyong Li, Eric D. Hsi, Yi Xia, Attilio Orazi, Xia, Y., Xu-Monette, Z. Y., Tzankov, A., Li, X., Manyam, G. C., Murty, V., Bhagat, G., Zhang, S., Pasqualucci, L., Visco, C., Dybkaer, K., Chiu, A., Orazi, A., Zu, Y., Richards, K. L., Hsi, E. D., Choi, W. W. L., Van Krieken, J. H., Huh, J., Ponzoni, M., Ferreri, A. J. M., Moller, M. B., Parsons, B. M., Winter, J. N., Piris, M. A., Westin, J., Fowler, N., Miranda, R. N., Ok, C. Y., Li, Y., Li, J., Medeiros, L. J., and Young, K. H.
- Subjects
0301 basic medicine ,Male ,Cancer Research ,Lymphoma ,Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] ,Biopsy ,medicine.disease_cause ,0302 clinical medicine ,immune system diseases ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,80 and over ,Sequence Deletion ,Regulation of gene expression ,Aged, 80 and over ,Mutation ,Tumor ,Hematology ,Genomics ,Middle Aged ,Prognosis ,Diffuse ,Gene Expression Regulation, Neoplastic ,Reconstructive and regenerative medicine Radboud Institute for Molecular Life Sciences [Radboudumc 10] ,medicine.anatomical_structure ,Adolescent ,Adult ,Aged ,Biomarkers, Tumor ,Female ,Follow-Up Studies ,Gene Expression Profiling ,Humans ,Lymphoma, Large B-Cell, Diffuse ,Neoplasm Staging ,Positive Regulatory Domain I-Binding Factor 1 ,Repressor Proteins ,Transcriptome ,Treatment Outcome ,Young Adult ,Oncology ,030220 oncology & carcinogenesis ,Lymphomas ,Bcl-2 protein family ,Biology ,Article ,03 medical and health sciences ,PRDM1 ,medicine ,Large B-Cell ,Journal Article ,B cell ,Neoplastic ,Germinal center ,medicine.disease ,Gene expression profiling ,030104 developmental biology ,Cancer--Genetic aspects ,Gene Expression Regulation ,Cancer research ,Diffuse large B-cell lymphoma ,Biomarkers - Abstract
Contains fulltext : 173033.pdf (Publisher’s version ) (Open Access) PRDM1/BLIMP-1, a master regulator of plasma-cell differentiation, is frequently inactivated in activated B-cell-like (ABC) diffuse large B-cell lymphoma (DLBCL) patients. Little is known about its genetic aberrations and relevant clinical implications. A large series of patients with de novo DLBCL was effectively evaluated for PRDM1/BLIMP-1 deletion, mutation, and protein expression. BLIMP-1 expression was frequently associated with the ABC phenotype and plasmablastic morphologic subtype of DLBCL, yet 63% of the ABC-DLBCL patients were negative for BLIMP-1 protein expression. In these patients, loss of BLIMP-1 was associated with Myc overexpression and decreased expression of p53 pathway molecules. In addition, homozygous PRDM1 deletions and PRDM1 mutations within exons 1 and 2, which encode for domains crucial for transcriptional repression, were found to show a poor prognostic impact in patients with ABC-DLBCL but not in those with germinal center B-cell-like DLBCL (GCB-DLBCL). Gene expression profiling revealed that loss of PRDM1/BLIMP-1 expression correlated with a decreased plasma-cell differentiation signature and upregulation of genes involved in B-cell receptor signaling and tumor-cell proliferation. In conclusion, these results provide novel clinical and biological insight into the tumor-suppressive role of PRDM1/BLIMP-1 in ABC-DLBCL patients and suggest that loss of PRDM1/BLIMP-1 function contributes to the overall poor prognosis of ABC-DLBCL patients.
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- 2016
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