Comprehensive CRISPR-Cas9 screens identify genetic determinants of drug responsiveness in multiple myeloma.

ABSTRACT: The introduction of new drugs in the past years has substantially improved outcome in multiple myeloma (MM). However, the majority of patients eventually relapse and become resistant to one or multiple drugs. While the genetic landscape of relapsed/ resistant multiple myeloma has been elucidated, the causal relationship between relapse-specific gene mutations and the sensitivity to a given drug in MM has not systematically been evaluated. To determine the functional impact of gene mutations, we performed combined whole-exome sequencing (WES) of longitudinal patient samples with CRISPR-Cas9 drug resistance screens for lenalidomide, bortezomib, dexamethasone, and melphalan. WES of longitudinal samples from 16 MM patients identified a large number of mutations in each patient that were newly

SUBMITTER: Bohl SR 

PROVIDER: S-EPMC8114551 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature