BCL6 suppression of BCL2 via Miz1 and its disruption in diffuse large B cell lymphoma

Masumichi Saito, Urban Novak, Erich Piovan, Katia Basso, Pavel Sumazin, Christof Schneider, Marta Crespo, Qiong Shen, Govind Bhagat, Andrea Califano, Amy Chadburn, Laura Pasqualucci, Riccardo Dalla-Favera

Research output: Contribution to journalArticle

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Abstract

The BCL6 proto-oncogene encodes a transcriptional repressor that is required for germinal center (GC) formation and whose deregulation by genomic lesions is implicated in the pathogenesis of GC-derived diffuse large B cell lymphoma (DLBCL) and, less frequently, follicular lymphoma (FL). The biological function of BCL6 is only partially understood because no more than a few genes have been functionally characterized as direct targets of BCL6 transrepression activity. Here we report that the anti-apoptotic proto-oncogene BCL2 is a direct target of BCL6 in GC B cells. BCL6 binds to the BCL2 promoter region by interacting with the transcriptional activator Miz1 and suppresses Miz1-induced activation of BCL2 expression. BCL6-mediated suppression of BCL2 is lost in FL and DLBCL, where the 2 proteins are pathologically coexpressed, because of BCL2 chromosomal translocations and other mechanisms, including Miz1 deregulation and somatic mutations in the BCL2 promoter region. These results identify an important function for BCL6 in facilitating apoptosis of GC B cells via suppression of BCL2, and suggest that blocking this pathway is critical for lymphomagenesis.

Original languageEnglish
Pages (from-to)11294-11299
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number27
DOIs
Publication statusPublished - Jul 7 2009

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Germinal Center
Lymphoma, Large B-Cell, Diffuse
Follicular Lymphoma
Proto-Oncogenes
Genetic Promoter Regions
B-Lymphocytes
Genetic Translocation
Critical Pathways
Apoptosis
Mutation
Genes
Proteins

Keywords

  • Apoptosis
  • DLBCL
  • Germinal center

ASJC Scopus subject areas

  • General

Cite this

BCL6 suppression of BCL2 via Miz1 and its disruption in diffuse large B cell lymphoma. / Saito, Masumichi; Novak, Urban; Piovan, Erich; Basso, Katia; Sumazin, Pavel; Schneider, Christof; Crespo, Marta; Shen, Qiong; Bhagat, Govind; Califano, Andrea; Chadburn, Amy; Pasqualucci, Laura; Dalla-Favera, Riccardo.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 27, 07.07.2009, p. 11294-11299.

Research output: Contribution to journalArticle

Saito, M, Novak, U, Piovan, E, Basso, K, Sumazin, P, Schneider, C, Crespo, M, Shen, Q, Bhagat, G, Califano, A, Chadburn, A, Pasqualucci, L & Dalla-Favera, R 2009, 'BCL6 suppression of BCL2 via Miz1 and its disruption in diffuse large B cell lymphoma', Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 27, pp. 11294-11299. https://doi.org/10.1073/pnas.0903854106
Saito, Masumichi ; Novak, Urban ; Piovan, Erich ; Basso, Katia ; Sumazin, Pavel ; Schneider, Christof ; Crespo, Marta ; Shen, Qiong ; Bhagat, Govind ; Califano, Andrea ; Chadburn, Amy ; Pasqualucci, Laura ; Dalla-Favera, Riccardo. / BCL6 suppression of BCL2 via Miz1 and its disruption in diffuse large B cell lymphoma. In: Proceedings of the National Academy of Sciences of the United States of America. 2009 ; Vol. 106, No. 27. pp. 11294-11299.
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