Mutant EZH2 Induces a Pre-malignant Lymphoma Niche by Reprogramming the Immune Response.
Cancer Cell
; 37(5): 655-673.e11, 2020 05 11.
Article
em En
| MEDLINE
| ID: mdl-32396861
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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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos B
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Transformação Celular Neoplásica
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Linfoma de Células B
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Linfoma Folicular
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Reprogramação Celular
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Proteína Potenciadora do Homólogo 2 de Zeste
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Mutação
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Cancer Cell
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2020
Tipo de documento:
Article