A genome-scale CRISPR knock-out screen in chronic myeloid leukemia identifies novel drug resistance mechanisms along with intrinsic apoptosis and MAPK signaling.

ABSTRACT: Understanding resistance mechanisms in cancer is of utmost importance for the discovery of novel "druggable" targets. Efficient genetic screening, now even more possible with CRISPR-Cas9 gene-editing technology, next-generation sequencing and bioinformatics, is an important tool for deciphering novel cellular processes, such as resistance to treatment in cancer. Imatinib specifically eliminates chronic myeloid leukemia (CML) cells by targeting and blocking the kinase activity of BCR-ABL1; however, resistance to treatment exists. In order to discover BCR-ABL1 independent mechanisms of imatinib resistance, we utilized the genome-scale CRISPR knock-out library to screen for imatinib-sensitizing genes in vitro on K562 cells. We revealed genes that seem essential for imatinib-induced cell death

SUBMITTER: Lewis M 

PROVIDER: S-EPMC7520295 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature