The transcriptional landscape of drug effects in CLL
Caroline Lohoff,Junyan Lu
Heidelberg University Hospital, Lu Group
Abstract
Despite extensive investigation of appropriate drugs for the treatment of CLL, the resulting transcriptional response remain incompletely understood. In this collaboration with the University Hospital Zurich and GeneCore we investigate the transcriptional landscape of drug effects in chronic lymphocytic leukemia (CLL) in a systematic and high-throughput manner. The data set consists of more than 1100 low depth 3‘-end RNAseq samples from more than 100 patients. The primary tumor samples were treated with DMSO as a control and ten drugs selected based on important pathways in CLL. Together with clinical and flow cytometry data, we aim to describe the mode-of-action of those drugs and to understand the patient-specific pathway changes associated with drug treatment. Furthermore, the large representative cohort will allow us to characterize the impact of different drugs in relation to molecular subgroups and the presence of genomic aberrations, such as IGHV mutational status or trisomy 12. The findings will serve as a reference to create a global pathway wiring map of CLL cells and identify biomarkers for drug resistance and combinatorial therapy. Several Bioconductor packages are used for the analysis.