Abstract 3: Targeting epigenetic modifiers in diffuse large B-cell lymphoma

Abstract

Abstract Diffuse Large B-Cell Lymphoma (DLBCL) is the most common type of Non-Hodgkin lymphoma, accounting for approximately 40% of all cases worldwide. In the last five years, researchers uncovered that DLBCL is characterized by widespread epigenetic deregulation. Lymphoma cells harbor loss-of-function mutations in transcriptional activators (KMT2D, EP300, CREBBP) and gain-of-function mutations in transcriptional repressors (EZH2). In our study, we aim to identify epigenetic vulnerabilities in lymphoma cells that can be targeted to deliver cytotoxic responses. We screened the therapeutic efficacy of a panel of lysine and arginine methyltransferase inhibitors in multiple lymphoma cell lines. Through these screens, we identified the Type I Protein Arginine Methyltransferase (PRMT) family as an attractive therapeutic target that induced cytotoxicity. Mechanistic dissection revealed that Type I PRMT inhibition caused apoptosis through deregulation of transcription factors and pro-survival genes. In addition, we uncovered novel crosstalk between PRMTs and other epigenetic modifiers that influenced cell fate in lymphoma. Our study demonstrates a critical role for Type I PRMTs in DLBCL, and adds a lucrative target to the growing list of promising epigenetics-based therapies. Citation Format: Aarthi Goverdhan, Heng-Huan Lee, Mien-Chie Hung. Targeting epigenetic modifiers in diffuse large B-cell lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3. doi:10.1158/1538-7445.AM2017-3