An In Vivo CRISPR Screening Platform for Prioritizing Therapeutic Targets in AML.

ABSTRACT: CRISPR-Cas9-based genetic screens have successfully identified cell type-dependent liabilities in cancer, including acute myeloid leukemia (AML), a devastating hematologic malignancy with poor overall survival. Because most of these screens have been performed in vitro using established cell lines, evaluating the physiologic relevance of these targets is critical. We have established a CRISPR screening approach using orthotopic xenograft models to validate and prioritize AML-enriched dependencies in vivo, including in CRISPR-competent AML patient-derived xenograft (PDX) models tractable for genome editing. Our integrated pipeline has revealed several targets with translational value, including SLC5A3 as a metabolic vulnerability for AML addicted to exogenous myo-inosit

SUBMITTER: Lin S 

PROVIDER: S-EPMC8831447 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature