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SOX11 defines two different subtypes of mantle cell lymphoma through transcriptional regulation of BCL6

Leukemia volume 30, pages 1596–1599 (2016)Cite this article

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Mantle cell lymphoma (MCL) is an aggressive lymphoid neoplasm initially considered as derived from naive, pre-germinal center lymphocytes.1 However, several studies have now shown that 15–40% of cases carry somatic mutations in the expressed immunoglobulin (IGVH) gene, indicating that at least a subset of MCL is derived from antigen-experienced cells that have transitioned through the germinal center (GC).2 The clinical impact of the IGHV mutational status on MCL has not been as well investigated as in chronic lymphocytic leukemia (CLL) but some studies have suggested a better outcome for patients with high load of IGHV mutations.3, 4, 5 Intriguingly, the presence of hypermutated IGVH in MCL has been associated with negative or low expression of SRY (sex-determining region Y)-box11 (SOX11) transcription factor.5, 6, 7 Global gene expression analysis of MCL has shown that IGHV-mutated/SOX11-negative cases have a profile enriched in memory B cells-related signatures compared with IGHV-unmutated/SOX11-positive tumors with a profile closer to naive B cells.5, 8 All these observations suggest that SOX11 may have a role in the differentiation process of the MCL cells through the GC and subsequently in the acquisition of IGHV somatic hypermutations (SHM).

To test this idea we revisited our previous chromatin Immunoprecipitation (ChIP)-chip experiments on MCL cell lines searching for potential SOX11 direct target genes that may explain the relationship between SOX11 expression and IGHV mutational status.8 In this analysis, we identified B-cell CLL/lymphoma 6 (BCL6) as one of the most significant targets of SOX11. BCL6 is a transcription factor essential for the GC formation. It is required during the intense proliferation that characterizes GC B cells to allow IGHV-SHM, and its downregulation is necessary for exiting the GC and follow the differentiation into memory B cells or plasma cells.9

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Acknowledgements

We are grateful to L Pasqualucci and R Dalla-Favera for providing the pLA/S5 reported construct and pMT2T-HA-BCL6 expressing plasmid. We are grateful to Giovanna Rocador from the Centro Nacional Investigación Oncológica, Madrid, Spain for generously providing us the BCL6 antibody. We are grateful to Xose S Puente for analyzing WGS and WES data. This study has been supported by the Ministerio de Economía y Competitividad (BFU2012-30857 to VA), Fundació La Marató de TV3-Cancer 2013 (20130110 to VA) and the Instituto de Salud Carlos III RTICC (RD12/0036/0036 and PIE13/00033 to EC). Fondo Europeo de Desarrollo Regional. Unión Europea. Una manera de hacer Europa. EC is an ICREA-Academia Researcher.

Author contributions

JP, MCV and AE performed experiments, analyzed data and wrote the manuscript; MLR, PB and DM performed experiments, EC and VA designed research and wrote the manuscript; and all authors reviewed and approved the manuscript.

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Author notes

  1. J Palomero, M C Vegliante and A Eguileor: These authors share authorship.

Authors and Affiliations

  1. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    J Palomero, M C Vegliante, A Eguileor, M L Rodríguez, P Balsas, E Campo & V Amador

  2. Hospital Clínic, University of Barcelona, Barcelona, Spain

    D Martínez & E Campo

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  1. J Palomero
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  2. M C Vegliante
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Correspondence to V Amador.

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Palomero, J., Vegliante, M., Eguileor, A. et al. SOX11 defines two different subtypes of mantle cell lymphoma through transcriptional regulation of BCL6. Leukemia 30, 1596–1599 (2016). https://doi.org/10.1038/leu.2015.355

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