Genetic determinants of venetoclax resistance

Resistance to the first approved BCL-2 inhibitor venetoclax is emerging in lymphoid malignancies. The study aimed to identify the genetic determinants of such resistance. From genome-scale screens we determined the genes influencing the sensitivity to BCL-2 inhibition. The present set of data is related to expression changes (assessed by RNA sequencing) observed in the resistant OCI-Ly1 lymphoma cell line as well as those resulting from genetic perturbation (using CRISPR-Cas9) targeting the genes highlighted in our genome-scale screen. Overall design: Expression changes (RNA sequencing data) of 32 engineered OCI-Ly1 cell lines (duplicates for each): venetoclax resistant, parental and CRISPR-Cas9 manipulated cell lines with 2 different sgRNA per target (non-targeting sgRNA, ID3-KO, NFKBIA-KO, IKZF5-KO, OTUD5-KO, UBR5-KO, EP300-KO). ATAC-seq of the ID3 OCI-Ly1 knockout (vs control) lines and of the OCI-Ly1-R vs OCI-Ly1-S (duplicates for each).