Heterologous promoters fused to BCL6 by chromosomal translocations affecting band 3q27 cause its deregulated expression during B-cell differentiation Journal Article
| Authors: | Chen, W.; Iida, S.; Louie, D. C.; Dalla-Favera, R.; Chaganti, R. S. K. |
| Article Title: | Heterologous promoters fused to BCL6 by chromosomal translocations affecting band 3q27 cause its deregulated expression during B-cell differentiation |
| Abstract: | The BCL6 gene encodes a POZ/Zinc-finger protein, which acts as a sequence-specific transcriptional repressor. It is expressed in B cells within the germinal centers (GC) and is required for GC formation. In ≃40% of diffuse large cell lymphomas (DLCL) and ≃14% of follicular lymphomas (FL), the BCL6 gene is rearranged by chromosomal translocations, which juxtapose heterologous promoters and 5' untranslated sequences derived from other chromosomes to the BCL6 coding domain or by mutations in the 5' regulatory region. To understand the functional consequence of the chromosomal translocations, we have studied the patterns of expression of the promoters found juxtaposed to BCL6 in DLCL and FL during B-lineage differentiation. Distinct heterologous 5' untranslated regions (IGH, IGL, TTF) were identified fused to the BCL6 coding domain by analysis of BCL6 cDNAs in two DLCL cases and one mixed follicular lymphoma (MxFL). These three sequences, as well as three other previously identified BCL6 fusion partners (IGHG3, BOB1, H4), were studied for their pattern of expression during B- lineage differentiation by Northern blot analysis of B-cell lines representative of the pro-B, B, immunoblast, and plasma cell stages. In contrast to BCL6, whose transcription is activated only in B cells within the GC, all of the other sequences displayed a broader pattern of expression ranging from constitutive expression throughout B-cell differentiation to persistent expression in immunoblasts and plasma cells. These results indicate that the expression of BCL6 is deregulated as a consequence of fusion to heterologous promotor regions. The persistent expression of activated BCL6 may contribute to lymphomagenesis by blocking B-cell differentiation within the GC. |
| Keywords: | immunohistochemistry; human tissue; human cell; promoter region; dna-binding proteins; proto-oncogene proteins; gene amplification; cell differentiation; b lymphocyte; b-lymphocytes; transcription factors; germinal center; plasma cell; gene expression regulation, neoplastic; lymphoma, b-cell; chromosome translocation; translocation, genetic; large cell lymphoma; zinc finger protein; follicular lymphoma; dna determination; b lymphocyte differentiation; chromosome 3q; northern blotting; chromosomes, human, pair 3; promoter regions (genetics); proto-oncogene proteins c-bcl-6; humans; human; priority journal; article; immunoblast |
| Journal Title: | Blood |
| Volume: | 91 |
| Issue: | 2 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 1998-01-15 |
| Start Page: | 603 |
| End Page: | 607 |
| Language: | English |
| PUBMED: | 9427715 |
| PROVIDER: | scopus |
| DOI: | 10.1182/blood.V91.2.603 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 12 December 2016 -- Source: Scopus |
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