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05.12.2016 | Original Article

BCL6 locus is hypermethylated in angioimmunoblastic T-cell lymphoma

verfasst von: Shoko Nishizawa, Mamiko Sakata-Yanagimoto, Keiichiro Hattori, Hideharu Muto, Tran Nguyen, Koji Izutsu, Kenichi Yoshida, Seishi Ogawa, Naoya Nakamura, Shigeru Chiba

Erschienen in: International Journal of Hematology | Ausgabe 4/2017

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Abstract

BCL6, a master transcription factor for differentiation of follicular helper T (TFH) cells, is highly expressed in angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphomas (PTCL) containing tumor cells with TFH features. TET2, encoding an epigenetic regulator, is frequently mutated in AITL/PTCL. We previously reported that Tet2 knockdown mice developed T-cell lymphomas with TFH features. Hypermethylation of the Bcl6 locus followed by BCL6 upregulation was thought to be the key event for lymphoma development in mice. The mechanisms by which BCL6 expression is upregulated in human AITL/PTCL, however, have not been elucidated. Here, we investigated the impact of TET2 mutations on methylation of BCL6 locus in human AITL/PTCL samples. Hypermethylation of the BCL6 locus was more frequent in PTCL samples than B-cell lymphoma samples (PTCL vs B-cell lymphomas: 9/42 vs 0/35). PTCL samples with TET2 mutations were more frequently hypermethylated than those without TET2 mutations (PTCL with TET2 mutations vs without mutations: 6/22 vs 0/17). BCL6 expression in hypermethylated samples was higher than that in low methylated samples. Deregulated BCL6 expression caused by hypermethylation and TET2 mutations may result in skewed TFH differentiation and eventually contribute to AITL/PTCL development in patients, as well as lymphoma development in Tet2 knockdown mice.

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Titel: BCL6 locus is hypermethylated in angioimmunoblastic T-cell lymphoma
verfasst von: Shoko Nishizawa
Mamiko Sakata-Yanagimoto
Keiichiro Hattori
Hideharu Muto
Tran Nguyen
Koji Izutsu
Kenichi Yoshida
Seishi Ogawa
Naoya Nakamura
Shigeru Chiba
Publikationsdatum: 05.12.2016
Verlag: Springer Japan
Erschienen in: International Journal of Hematology / Ausgabe 4/2017
Print ISSN: 0925-5710
Elektronische ISSN: 1865-3774
DOI: https://doi.org/10.1007/s12185-016-2159-z

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BCL6 locus is hypermethylated in angioimmunoblastic T-cell lymphoma

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