The role of EZH2 dysregulation in the pathogenesis of B-cell lymphomas and its implications as a target therapy

B-cell lymphomas are a group of heterogeneic diseases. During B-cell development, the germinal center (GC) reaction is a complex process, in which transcripcional programs have an epigenetic regulation. Enhancer of zeste homologue-2 (EZH2) is a histone methyltransferase, which catalyzes trimethylation of histone H3 at lysine 27 (H3K27me3) to control gene transcription critical for cell proliferation, function, differentiation and expansion. It controls the normal biology of germinal B cells. Epigenetic dysregulation is a hallmark of Diffuse large B- cell lymphoma (DLBCL) and follicular lymphoma (FL), with gain of function (GOF) EZH2 mutations. EZH2 is also overexpressed and plays an important role in lymphomagenesis. Follicular lymphoma (FL) pathogenesis includes epigenomic alterations affecting the immunological niche, and their potential consequences on the informational transfer between the microenvironment and tumor B cells. The introduction of novel target therapies and immunotherapeutics modalities in B cell lymphomas has shifted the treatment landscape. Tazemetostat received FDA approval as the first epigenetic therapy for FL. Valemetostat, which inhibits EZH1/2, as well as tazemetostat in combination with other drugs have been subject of recent research. The purpose of this article is to review the role of EZH2 in normal B cell differentiation and in the pathogenesis of B-Cell lymphomas.