Genome-scale drop-out screens to identify cancer cell vulnerabilities in AML

Abstract

Acute myeloid leukemia (AML) is an aggressive cancer that remains lethal to the majority of sufferers. Whilst the mainstay treatments for this condition have remained largely unchanged over the past five decades, progress in deciphering its pathogenesis has accelerated in recent years, propelled in part by advances in cancer genomics and mechanistic studies of leukemogenic mutations. Newer molecular therapies targeting aberrant biological pathways are currently under investigation with a few moving closer to clinical use. However, collectively, these new therapies are not predicted to have a major impact on clinical outcomes and the need for the identification of further therapeutic targets in AML remains critical. Recently the use of CRISPR-Cas9 systems for genome editing and their potential application in genome-wide screening has opened a new frontier for unbiased discovery of therapeutic vulnerabilities in cancer and AML was the first disease in which this technology was systematically applied. In this review we give an overview of recent advances in identifying novel therapeutic vulnerabilities of AML using CRISPR-Cas9 and discuss possible future applications of CRISPR technologies in this field.