High-throughput RNA sequencing transcriptome analysis of ABC-DLBCL reveals several tumor evasion strategies

Abstract

Activated B-cell (ABC) lymphoma, a distinct molecular entity within diffuse large B-cell lymphoma (DLBCL), remains highly incurable, showing a worse response to standard immunochemotherapy. The discouraging results obtained in several clinical trials using proteasome inhibitors, tyrosine kinase inhibitors, or immunomodulators, lead to an intense search for new, potentially druggable biomarkers in DLBCL. In this study, we designed an experimental strategy for DLBCL to discover high- and low-abundance RNA-seq-derived transcripts involved in the oncogenic phenotype in patients diagnosed with ABC-DLBCL. Based on the results of a comparative analysis, 79 DE genes and two enriched gene sets related to metabolism and immunity were selected. Genes related to drug resistance, anti-inflammatory response, and tumor-cell dissemination were found to be up-regulated, while tumor suppressor genes were down-regulated. Then, we searched for the perturbagens most suitable for gene expression profiling (GEP) by iLINCS-CMap. Herein, we present a novel experimental approach that connects the omics signature of DLBCL with potential drugs for more accurate treatments.