Genetic determinants of venetoclax resistance. 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).

淋巴系统恶性肿瘤中，首款获批的BCL-2抑制剂维奈克拉（venetoclax）的耐药性正逐渐显现。本研究旨在明确此类耐药性的遗传决定因素。我们通过全基因组筛选，确定了影响BCL-2抑制剂敏感性的相关基因。本数据集涵盖耐药OCI-Ly1淋巴瘤细胞系中的基因表达变化（经RNA测序评估），以及靶向全基因组筛选所得基因、经CRISPR-Cas9遗传扰动后产生的表达变化。

整体实验设计：32株工程改造的OCI-Ly1细胞系的表达变化（RNA测序数据，每个样本设置生物学重复）：包括维奈克拉耐药株、亲本株，以及经CRISPR-Cas9编辑的细胞系，每个靶基因使用2条向导RNA（sgRNA），分别为非靶向sgRNA、ID3基因敲除（ID3-KO）、NFKBIA基因敲除（NFKBIA-KO）、IKZF5基因敲除（IKZF5-KO）、OTUD5基因敲除（OTUD5-KO）、UBR5基因敲除（UBR5-KO）、EP300基因敲除（EP300-KO）。此外还包含ID3基因敲除的OCI-Ly1细胞系（与对照细胞系相比）以及OCI-Ly1-R（耐药株）与OCI-Ly1-S（敏感株）的ATAC测序（ATAC-seq）数据，每组均设置生物学重复。