CRISPR screen of venetoclax response-associated genes identifies transcription factor ZNF740 as a key functional regulator.

ABSTRACT: BCL-2 inhibitors such as venetoclax offer therapeutic promise in acute myeloid leukemia (AML) and other cancers, but drug resistance poses a significant challenge. It is crucial to understand the mechanisms that regulate venetoclax response. While correlative studies have identified numerous genes linked to venetoclax sensitivity, their direct impact on the drug response remains unclear. In this study, we targeted around 1400 genes upregulated in venetoclax-sensitive primary AML samples and carried out a CRISPR knockout screen to evaluate their direct effects on venetoclax response. Our screen identified the transcription factor ZNF740 as a critical regulator, with its expression consistently predicting venetoclax sensitivity across subtypes of the FAB classification. ZNF740 depletion lead

SUBMITTER: Zhang L 

PROVIDER: S-EPMC11350041 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature