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. We assessed a large cohort of patients with de novo DLBCL 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 tumor-suppressor molecules. Also, we found that homozygous PRDM1 deletions and PRDM1 mutations within exons 1 and 2 which encode for domains crucial for transcriptional repression had a poor prognostic impact in patients with ABC-DLBCL but not those with germinal center B-cell-like 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 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.Leukemia accepted article preview online, 29 August 2016. doi:10.1038/leu.2016.243.
Originalsprog | Engelsk |
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Tidsskrift | Leukemia |
Vol/bind | 31 |
Udgave nummer | 3 |
Sider (fra-til) | 625-636 |
ISSN | 0887-6924 |
DOI | |
Status | Udgivet - 2017 |