CRISPR-Cas9 screen reveals histone-3 methylation as sensitizer for dimethyl fumarate-induced death of malignant T cells

Constitutive activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) pathway is a hallmark of many lymphocyte-related cancers, including the cutaneous T cell lymphoma (CTCL) and its leukemic variant, the Sezary Syndrome. Dimethyl fumarate (DMF) has been identified as a promising NF-kB-targeted therapy and has shown positive outcomes in a phase II clinical trial involving patients with Sezary Syndrome. However, the development of resistance remains a significant challenge. Through a genome-wide CRISPR-Cas9 screen, we identified new genetic targets to overcome these barriers.