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  • Original Paper
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Ambivalent role of BCL6 in cell survival and transformation

Abstract

The BCL6 gene is often structurally altered and probably ‘misregulated’ in two different types of human B-cell non-Hodgkin lymphomas (BNHL) thought to arise from germinal centre B cells. BCL6 encodes a BTB/POZ and zinc finger protein whose biochemical properties support a role as a DNA-binding transcriptional repressor and disclose, in part, the underlying mechanisms. In contrast, the study of the ‘oncogenic’ structural alterations of BCL6 in BNHL and of its cellular functions gives rise to much more heterogeneous data with no obvious unifying picture so that how and even whether BCL6 contributes to lymphomagenesis remains unclear. This review will summarize the current knowledge about the ‘oncogenic’ alterations and cellular functions of BCL6 and, based on some results, will propose the following hypotheses: (1) In various systems, including in memory T cells and also in germinal centre B cells and possibly in certain postmitotic cells, BCL6 may act by stabilizing a particular stage of differentiation. (2) Both its ambivalent effects on cell survival and the heterogeneous consequences of its alterations in BNHL suggest that BCL6 can be oncogenic not only upon overexpression or persistent expression, as often proposed, but also, similar to some of its relatives, upon ‘accidental’ downregulation.

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Acknowledgements

I warmly thank Dr Alex Dent for insightful comments and sharing unpublished data, Drs Takeshi Tokuhisa, Alex Dent, Yuichi Nakamura, Hélène Pelczar and Patrick Martin for a critical reading of the manuscript, and to Dr Christophe Pivot-Pajot for suggestions. I am also very grateful to Dr Sophie Green-Rousseaux for her precious help with the language. This work was supported by grants from Centre National de la Recherche Scientifique (CNRS), Association pour la Recherche sur le Cancer (ARC) and Ligue contre le Cancer, comité du Val de Marne.

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Correspondence to Olivier Albagli-Curiel.

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Albagli-Curiel, O. Ambivalent role of BCL6 in cell survival and transformation. Oncogene 22, 507–516 (2003). https://doi.org/10.1038/sj.onc.1206152

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