Suppression of B-cell development genes is key to glucocorticoid efficacy in treatment of acute lymphoblastic leukemia.

ABSTRACT: Glucocorticoids (GCs), including dexamethasone (dex), are a central component of combination chemotherapy for childhood B-cell precursor acute lymphoblastic leukemia (B-ALL). GCs work by activating the GC receptor (GR), a ligand-induced transcription factor, which in turn regulates genes that induce leukemic cell death. Which GR-regulated genes are required for GC cytotoxicity, which pathways affect their regulation, and how resistance arises are not well understood. Here, we systematically integrate the transcriptional response of B-ALL to GCs with a next-generation short hairpin RNA screen to identify GC-regulated "effector" genes that contribute to cell death, as well as genes that affect the sensitivity of B-ALL cells to dex. This analysis reveals a pervasive role for GCs in suppressio

SUBMITTER: Kruth KA 

PROVIDER: S-EPMC5454339 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature