Loss of PRDM1/BLIMP-1 function contributes to poor prognosis of activated B-cell-like diffuse large B-cell lymphoma.
dc.contributor.author | Xia, Y | |
dc.contributor.author | Xu-Monette, ZY | |
dc.contributor.author | Tzankov, A | |
dc.contributor.author | Li, X | |
dc.contributor.author | Manyam, GC | |
dc.contributor.author | Murty, V | |
dc.contributor.author | Bhagat, G | |
dc.contributor.author | Zhang, S | |
dc.contributor.author | Pasqualucci, L | |
dc.contributor.author | Visco, C | |
dc.contributor.author | Dybkaer, K | |
dc.contributor.author | Chiu, A | |
dc.contributor.author | Orazi, A | |
dc.contributor.author | Zu, Y | |
dc.contributor.author | Richards, KL | |
dc.contributor.author | Hsi, ED | |
dc.contributor.author | Choi, WWL | |
dc.contributor.author | van Krieken, JH | |
dc.contributor.author | Huh, J | |
dc.contributor.author | Ponzoni, M | |
dc.contributor.author | Ferreri, AJM | |
dc.contributor.author | Møller, MB | |
dc.contributor.author | Parsons, BM | |
dc.contributor.author | Winter, JN | |
dc.contributor.author | Piris, MA | |
dc.contributor.author | Westin, J | |
dc.contributor.author | Fowler, N | |
dc.contributor.author | Miranda, RN | |
dc.contributor.author | Ok, CY | |
dc.contributor.author | Li, Y | |
dc.contributor.author | Li, J | |
dc.contributor.author | Medeiros, LJ | |
dc.contributor.author | Young, KH | |
dc.date.accessioned | 2019-09-21T21:12:20Z | |
dc.date.available | 2019-09-21T21:12:20Z | |
dc.date.issued | 2017-03 | |
dc.date.updated | 2019-09-21T21:12:19Z | |
dc.description.abstract | 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. | |
dc.identifier | leu2016243 | |
dc.identifier.issn | 0887-6924 | |
dc.identifier.issn | 1476-5551 | |
dc.identifier.uri | ||
dc.language | eng | |
dc.publisher | Springer Science and Business Media LLC | |
dc.relation.ispartof | Leukemia | |
dc.relation.isversionof | 10.1038/leu.2016.243 | |
dc.subject | Humans | |
dc.subject | Repressor Proteins | |
dc.subject | Antineoplastic Combined Chemotherapy Protocols | |
dc.subject | Biopsy | |
dc.subject | Neoplasm Staging | |
dc.subject | Prognosis | |
dc.subject | Treatment Outcome | |
dc.subject | Follow-Up Studies | |
dc.subject | Gene Expression Profiling | |
dc.subject | Gene Expression Regulation, Neoplastic | |
dc.subject | Sequence Deletion | |
dc.subject | Mutation | |
dc.subject | Adolescent | |
dc.subject | Adult | |
dc.subject | Aged | |
dc.subject | Aged, 80 and over | |
dc.subject | Middle Aged | |
dc.subject | Female | |
dc.subject | Male | |
dc.subject | Lymphoma, Large B-Cell, Diffuse | |
dc.subject | Young Adult | |
dc.subject | Transcriptome | |
dc.subject | Biomarkers, Tumor | |
dc.subject | Positive Regulatory Domain I-Binding Factor 1 | |
dc.title | Loss of PRDM1/BLIMP-1 function contributes to poor prognosis of activated B-cell-like diffuse large B-cell lymphoma. | |
dc.type | Journal article | |
duke.contributor.orcid | Xu-Monette, ZY|0000-0002-7615-3949 | |
duke.contributor.orcid | Young, KH|0000-0002-5755-8932 | |
pubs.begin-page | 625 | |
pubs.end-page | 636 | |
pubs.issue | 3 | |
pubs.organisational-group | School of Medicine | |
pubs.organisational-group | Duke | |
pubs.organisational-group | Pathology | |
pubs.organisational-group | Clinical Science Departments | |
pubs.publication-status | Published | |
pubs.volume | 31 |
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