Table 1. List of epigenetic therapy approaches for DLBCL.

Drugs	Site of Action	Goals	DLBCLS to Treat*
DNMTi (demethylating dose only)	Sites of focal hypermethylation Site of focal or diffuse epigenetic heterogeneity	Reverse methylation of tumor suppressors Reverse methylation of genes linked to chemo-resistance Erase heterogeneity, reduce clonality	Patients with SMAD1 or CDKN2A methylation Relapsed or newly diagnosed high risk patients
HDACi	Enhancer and promoter H3K9, H3K18, H3K27 acetylation >1000 non-histone proteins	Reverse centroblast enhancer poising Alter the functions of TP53, BCL6, NFkB, etc.	Mutant EP300 and CREBBP: marker for sensitivity or resistance?
EZH2i	“Locked-in” bivalent chromatin domains	Restore expression of proliferation checkpoint and differentiation genes	GCB type DLBCLs with or without EZH2 mutations Possible biomarkers: H3K27me3, EZH2 target gene signature
BCL6i	BCL6 target promoters and enhancers, including bivalent domains and poised enhancers	Induce cell death and proliferation arrest	GCB and ABC-DLBCLs, possibly those with BCL6 target gene signature

^*No biomarkers for these drugs are currently validated. This list is speculative based on publications discussed in the text.