Genomic deregulation of PRMT5 supports growth and stress tolerance in chronic lymphocytic leukemia.

ABSTRACT: Patients suffering from chronic lymphocytic leukemia (CLL) display highly diverse clinical courses ranging from indolent cases to aggressive disease, with genetic and epigenetic features resembling this diversity. Here, we developed a comprehensive approach combining a variety of molecular and clinical data to pinpoint translocation events disrupting long-range chromatin interactions and causing cancer-relevant transcriptional deregulation. Thereby, we discovered a B cell specific cis-regulatory element restricting the expression of genes in the associated locus, including PRMT5 and DAD1, two factors with oncogenic potential. Experimental PRMT5 inhibition identified transcriptional programs similar to those in patients with differences in PRMT5 abundance, especially MYC-driven and stress r

SUBMITTER: Schnormeier AK 

PROVIDER: S-EPMC7299935 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature