B cell lymphoma could be linked to inactivation of the PR domain containing 1 with zinc finger domain (PRDM1)/B lymphocyte-induced maturation protein 1 (BLIMP1) gene

08-21-2006

According to a study from the United States, "PRDM1/BLIMP1 is a transcriptional repressor expressed in a subset of germinal center (GC) B cells and in all plasma cells, and required for terminal B cell differentiation. The BLIMP1 locus lies on chromosome 6q21-q22.1, a region frequently deleted in B cell lymphomas, suggesting that it may harbor a tumor suppressor gene."

"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," explained L. Pasqualucci and colleagues, Columbia University. "BLIMP1 alterations included gene truncations, nonsense mutations, frameshift deletions, and splice site mutations that generate aberrant transcripts encoding truncated BLIMP1 proteins.

"In all cases studied, both BLIMP1 alleles were inactivated by deletions or mutations. Furthermore, most non-GC type DLBCL cases (n=20/26, 77%) lack BLIMP1 protein expression, despite the presence of BLIMP1 mRNA. These results indicate that a sizable fraction of ABC-DLBCL carry an inactive BLIMP1 gene, and suggest that the same gene is inactivated by epigenetic mechanisms in an additional large number of cases."

The researchers concluded, "These findings point to a role for BLIMP1 as a tumor suppressor gene, whose inactivation may contribute to lymphomagenesis by blocking post-GC differentiation of B cells toward plasma cells."

Pasqualucci and colleagues published the results of their research in the Journal of Experimental Medicine (Inactivation of the PRDM1/BLIMP1 gene in diffuse large B cell lymphoma. J Exp Med, 2006;203(2):311-317).

For additional information, contact L. Pasqualucci, Columbia University, Institute Cancer Genetics, New York City, NY 10032, USA.

This article was prepared by Cancer Gene Therapy Week editors from staff and other reports. Copyright 2006, Cancer Gene Therapy Week via NewsRx.com.