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Journal articles
Mutant EZH2 Induces a Pre-malignant Lymphoma Niche by Reprogramming the Immune Response
Wendy Beguelin
1, *
Matt Teater
1
Cem Meydan
1
Kenneth B. Hoehn
2
Jude M. Phillip
1
Alexey A. Soshnev
3
Leandro Venturutti
1
Martin A. Rivas
1
Maria T. Calvo-Fernandez
1
Johana Gutierrez
1
Jeannie M. Camarillo
4
Katsuyoshi Takata
5
Karin Tarte
6
Neil L. Kelleher
4
Christian Steidl
5
Christopher E. Mason
1, 7
Olivier Elemento
1
C. David Allis
3
Steven H. Kleinstein
2
Ari M. Melnick
1, *
*
Corresponding author
Wendy Beguelin 1
Correspondent author
Matt Teater 1
Author
Cem Meydan 1
Author
Kenneth B. Hoehn 2
Author
Jude M. Phillip 1
Author
Alexey A. Soshnev 3
Author
Leandro Venturutti 1
Author
Martin A. Rivas 1
Author
Maria T. Calvo-Fernandez 1
Author
Johana Gutierrez 1
Author
Jeannie M. Camarillo 4
Author
Katsuyoshi Takata 5
Author
Karin Tarte 6
Author
Neil L. Kelleher 4
Author
Christian Steidl 5
Author
Christopher E. Mason 1, 7
Author
Olivier Elemento 1
Author
C. David Allis 3
Author
Steven H. Kleinstein 2
Author
Ari M. Melnick 1
Correspondent author
1
Cornell University [New York] ( Ithaca, New York 14853 - United States)
2
Yale University School of Medicine (Yale University School of Medicine, New Haven, Connecticut - United States)
3
Rockefeller University [New York] (1230 York Ave, New York, NY 10065, États-Unis - United States)
4
Northwestern University [Evanston] (633 Clark Street, Evanston, IL 60208 Evanston - United States)
5
British Columbia (Canada)
6
MICMAC - Microenvironment, Cell Differentiation, Immunology and Cancer (INSERM UMR1236, Campus Santé, Bât 2, Université de Rennes 1, 2 Avenue du Professeur Léon Bernard, 35043 Rennes, France - France)
- UR1 - Université de Rennes 1 (2 rue du Thabor - CS 46510 - 35065 Rennes cedex - France)
- UNIV-RENNES - Université de Rennes (France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1236 (101, rue de Tolbiac, 75013 Paris - France)
- Biosit : Biologie - Santé - Innovation Technologique - Structure Fédérative de Recherche en Biologie et Santé de Rennes (Université Rennes 1 - Campus Santé Villejean - 2, avenue Professeur Léon Bernard 35043 Rennes cedex - France)
7
Weill Medical College of Cornell University [New York] (Manhattan - United States)
Abstract : Follicular lymphomas (FLs) are slow-growing, indolent tumors containing extensive follicular dendritic cell (FDC) networks and recurrent EZH2 gain-of-function mutations. Paradoxically, FLs originate from highly proliferative germinal center (GC) B cells with proliferation strictly dependent on interactions with T follicular helper cells. Herein, we show that EZH2 mutations initiate FL by attenuating GC B cell requirement for T cell help and driving slow expansion of GC centrocytes that become enmeshed with and dependent on FDCs. By impairing T cell help, mutant EZH2 prevents induction of proliferative MYC programs. Thus, EZH2 mutation fosters malignant transformation by epigenetically reprograming B cells to form an aberrant immunological niche that reflects characteristic features of human FLs, explaining how indolent tumors arise from GC B cells.
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Journal articles
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https://hal-univ-rennes1.archives-ouvertes.fr/hal-02797079
Contributor : Laurent Jonchère <>
Submitted on : Friday, June 5, 2020 - 2:27:34 PM
Last modification on : Friday, June 11, 2021 - 5:12:08 PM
Contributor : Laurent Jonchère <>
Submitted on : Friday, June 5, 2020 - 2:27:34 PM
Last modification on : Friday, June 11, 2021 - 5:12:08 PM
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Identifiers
- HAL Id : hal-02797079, version 1
- DOI : 10.1016/j.ccell.2020.04.004
- PUBMED : 32396861
Collections
UNIV-RENNES1 | U917 | BIOSIT | UR1-UFR-SVE | MICMAC | UNIV-RENNES
Citation
Wendy Beguelin, Matt Teater, Cem Meydan, Kenneth B. Hoehn, Jude M. Phillip, et al.. Mutant EZH2 Induces a Pre-malignant Lymphoma Niche by Reprogramming the Immune Response. Cancer Cell, Elsevier, 2020, 37 (5), pp.655-+. ⟨10.1016/j.ccell.2020.04.004⟩. ⟨hal-02797079⟩
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