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Review
. 2019 Oct;14(5):439-450.
doi: 10.1007/s11899-019-00541-9.

Chromatin-Remodeled State in Lymphoma

Yuxuan Liu  1 , Yulissa Gonzalez  1 , Jennifer E Amengual  2
Affiliations
Review

Chromatin-Remodeled State in Lymphoma

Yuxuan Liu et al. Curr Hematol Malig Rep. 2019 Oct.

Abstract

Purpose of review: Emerging evidence has shown that epigenetic derangements might drive and promote tumorigenesis in various types of malignancies and is prevalent in both B cell and T cell lymphomas. The purpose of this review is to explain how the epigenetic derangements result in a chromatin-remodeled state in lymphoma and contribute to the biology and clinical features of these tumors.

Recent findings: Studies have explored on the functional role of epigenetic derangements in chromatin remodeling and lymphomagenesis. For example, the haploinsufficiency of CREBBP facilitates malignant transformation in mice and directly implicates the importance to re-establish the physiologic acetylation level. New findings identified 4 prominent DLBCL subtypes, including EZB-GC-DLBCL subtype that enriched in mutations of CREBBP, EP300, KMT2D, and SWI/SNF complex genes. EZB subtype has a worse prognosis than other GCB-tumors. Moreover, the action of the histone modifiers as well as chromatin-remodeling factors (e.g., SWI/SNF complex) cooperates to influence the chromatin state resulting in transcription repression. Drugs that alter the epigenetic landscape have been approved in T cell lymphoma. In line with this finding, epigenetic lesions in histone modifiers have recently been uncovered in this disease, further confirming the vulnerability to the therapies targeting epigenetic derangements. Modulating the chromatin state by epigenetic-modifying agents provides precision-medicine opportunities to patients with lymphomas that depend on this biology.

Keywords: Chromatin; Epigenetics; Lymphoma.

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Conflict of interest statement

Conflict of Interest: Dr. Amengual declares that she has received a grant from Appia Pharmaceuticals and has been paid to speak by Epizyme. Dr. Yuxuan and Dr. Rosario have no conflicts to disclose.

Figures

Figure 1:
Figure 1:
Epigenetic regulation of the chromatin state. Three main groups of enzymes and proteins control these processes: writers, erasers, and readers. Me=Fmethylation, Ac=acetylation, Ub= ubiquitination, SWI/SNF=switch/sucrose non-fermentable.
Figure 2:
Figure 2:
Interplay between EZH2 and MLL2 in normal hematopoietic cells
Figure 3:
Figure 3:
As part of the COMPASS complex, KMT2D has a role as a SET1 methyltransferase leading to the monomethylation of H3K4, which opposes H3k27me3. UTX, part of the KMT2D/COMPASS complex, is a demthylase responsible for the demethylation of H3K4. Removal of the H3K4 methyl group, allows for trimethylation of H3K27me3 by the EZH2/PRC2 complex.
See this image and copyright information in PMC

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