Epigenomic profiling of glucocorticoid responses identifies cis-regulatory disruptions impacting steroid resistance in childhood acute lymphoblastic leukemia.

ABSTRACT: Glucocorticoids (GCs) are a mainstay of contemporary, multidrug chemotherapy in the treatment of childhood acute lymphoblastic leukemia (ALL), and resistance to GCs remains a major clinical concern. Resistance to GCs is predictive of ALL relapse and poor clinical outcome, and therefore represents a major hurdle limiting further improvements in survival rates. While advances have been made in identifying genes implicated in GC resistance, there remains an insufficient understanding of the impact of cis-regulatory disruptions in resistance. To address this, we mapped the gene regulatory response to GCs in two ALL cell lines using functional genomics and high-throughput reporter assays and identified thousands of GC-responsive changes to chromatin state, including the formation of over 250 GC

SUBMITTER: Bergeron BP 

PROVIDER: S-EPMC9522591 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature