Abstract 2077: DLEU1 significantly alters programmed cell death in chemoimmunotherapy-treated TALENs-induced DLEU1 knockout and DLEU1 overexpressing Burkitt Lymphoma (BL): DLEU1 may act as a tumor suppressor gene in pediatric BL

BACKGROUND:Burkitt Lymphoma (BL) is the most common histological subtype of childhood and adolescent Non Hodgkin Lymphoma (Cairo et al, Blood 2007; Miles/Cairo, BJH 2012). Pediatric patients with BL with a chromosome 13q deletion, particularly 13q14.3, had significantly poorer outcome and inferior overall survival despite aggressive short, intensive multi-agent chemotherapy (Poirel/Cairo et al, Leukemia 2009; Nelson/Cairo/Sanger et al, BJH 2009). Deleted in Lymphocytic Leukemia 1 (DLEU1) is a BL classifier gene in the 13q14.3 (Dave et al, NEJM 2006) and it has been implicated in regulating programmed cell death in patients. Sequence-specific Transcription Activator-Like Effector Nucleases (TALENs) have been developed for precision targeted genome editing in in vitro and in vivo (Sander et al, Nat Bio 2011).OBJECTIVES:We hypothesize that DLEU1 may act as a tumor suppressor gene and therefore investigated whether DLEU1 expression results in changes in gene expression profiles, cell viability, apoptosis induced by chemoimmunotherapy regimens in DLEU1 knockout and/or DLEU1 overexpressing Raji BL cells.METHODS:TALEN-mediated DLEU1 knockout (DLEU1-KO) and DLEU1 overexpressing Raji BL cells (DLEU1-OE) were treated with Rituximab (RTX) and/or Cyclophosphamide (CTX). MTS, Caspase assay, qRT-PCR, western blot, and gene expression profiling using Affymetrix HG-133+ 2.0 arrays were performed.RESULTS:A significant decrease of apoptosis in DLEU1-KO (32.5±11.8%, p
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Molecular and Cellular Biology Source Type: research