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 forBLIMP-1 protein expression.
The tumor suppressors B-lymphocyte-induced maturation protein-1 (BLIMP-1) and p53 play a crucial role in B-cell lymphomas, and their inactivation contributes to the pathogenesis of a wide spectrum of lymphoid malignancies, including diffuse large B-cell lymphomas (DLBCLs).
Discordance of PRDM1 messenger RNA and protein expressions is associated with high EBV-miR-BHRF1-2 levels in LCLs and primary post-transplant EBV-positive DLBCL.
BLIMP1 is frequently inactivated in a variety of lymphomas, including diffuse large B cell lymphomas, Natural Killer cell lymphoma and anaplastic large T cell lymphoma.
PRDM1/Blimp1 is a master regulator of terminal B cell differentiation and may also function as a tumor suppressor in the pathogenesis of DLBCL, where it is frequently inactivated by mutations and deletions.
Thus, abnormal epigenetic down-regulation of PRDM1 by let-7 and other microRNAs may represent an alternative mechanism of reducing normal PRDM1 function in a subset of DLBCL with relatively high PRDM1alpha mRNA expression and unmutated PRDM1.
Taken together with previous reports, the present results suggest that two key transcription factors for the plasmacytic differentiation, XBP1 and BLIMP1, are involved in the pathogenesis in diffuse large B-cell lymphoma.
PRDM1/Blimp-1, a master regulator in terminal B-cell differentiation, has been recently identified as a tumor suppressor target for mutational inactivation in diffuse large B-cell lymphomas of the activated B-cell type.
PRDM1 protein expression was recently demonstrated in a subset of diffuse large B-cell lymphoma (DLBCL) with aggressive behavior, a type of lymphoma for which rituximab associated with chemotherapy (R-CHOP) is now widely indicated.
Here, we describe novel mutations in the BLIMP1 gene in 2 of 15 (13%) cases of B-cell lymphoma (two cases of primary effusion lymphoma and 13 cases of diffuse large B-cell lymphoma).
Unexpectedly, a subset of diffuse large B-cell lymphoma expressed PRDM1, lacked detectable plasmablastic or immunoblastic changes and displayed more aggressive behavior, with a shorter failure-free survival.
This study identifies PRDM1 inactivation as a recurrent genetic defect in DLBCL cells and establishes PRDM1 as a potential tumor suppressor gene in DLBCL.
We report here that the BLIMP1 gene is inactivated by structural alterations in 24% (8 out of 34) activated B cell-like diffuse large cell lymphoma (ABC-DLBCL), but not in GC B cell-like (n = 0/37) or unclassified (n = 0/21) DLBCL.