EPIGENETIC BASIS AND THERAPY OF DLBCL

Somatic mutations of transcription factors and chromatin modifiers are a genetic hallmark DLBCLs regardless subtype. Most arise from B cells transiting the germinal center reaction during humoral immune response. During this process undergo series rapid phenotypic changes, induce through synapse they form with specialized T follicular helper (THF cells). their proliferative burst, B-cells downregulate many genes which allows them to somatic hypermutation without interruption. that impair expression subsets lead development GCB-DLBCLs, whereas hijack enhance ABC-DLBCLs. In GCB-DLBCLs impaired is often due in EZH2, CREBBP, KMT2D, ARID1A, etc. Each these have specific distinct biochemical functions caused somewhat different phenotypes cause evasion shape lymphoma microenvironment ways. Novel selective therapeutic agents now exist counteract each four classes modifiers, enable system re-engage kill lymphomas potently activity immunotherapies, if properly sequenced dosed may profound anti-lymphoma activity. Although not mutated ABC-DLBCL, effect canonical signaling such as MYD88L256P ultimately mediate effects by reprogramming epigenome cells, favoring emergence aberrant transcriptional programs, TBET autoimmune cell program. These mechanisms also provide opportunities for novel epigenetic interventions. Here, we will review concepts view towards how be eradicated re-establishing proper control surveillance other functions. Keywords: genomics, epigenomics, -omics, tumor biology heterogeneity No conflicts interests pertinent abstract.