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Heterologous Promoters Fused to BCL6 by Chromosomal
Translocations Affecting Band 3q27 Cause Its Deregulated Expression
During B-Cell Differentiation
Weiyi Chen,
Shinsuke Iida,
Diane C. Louie,
Riccardo Dalla-Favera, and
R.S.K. Chaganti
From the Cell Biology Program and The Departments of Human Genetics
and Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY;
and the Division of Oncology, Department of Pathology, College of
Physicians and Surgeons, Columbia University, New York, NY.
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 pre-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 promoter regions. The persistent expression of activated BCL6 may contribute to lymphomagenesis by blocking B-cell differentiation within the GC.
Blood, Vol. 91 No. 2 (January 15), 1998:
pp. 603-607
© 1998 by The American Society of Hematology.
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