ESRRB regulates glucocorticoid gene expression in mice and patients with acute lymphoblastic leukemia.

ABSTRACT: Synthetic glucocorticoids (GCs), such as dexamethasone and prednisone, remain key components of therapy for patients with lymphoid malignancies. For pediatric patients with acute lymphoblastic leukemia (ALL), response to GCs remains the most reliable prognostic indicator; failure to respond to GC correlates with poor event-free survival. To uncover GC resistance mechanisms, we performed a genome-wide, survival-based short hairpin RNA screen and identified the orphan nuclear receptor estrogen-related receptor-β (ESRRB) as a critical transcription factor that cooperates with the GC receptor (GR) to mediate the GC gene expression signature in mouse and human ALL cells. Esrrb knockdown interfered with the expression of genes that were induced and repressed by GR and resulted in GC resistance i

SUBMITTER: Gallagher KM 

PROVIDER: S-EPMC7362368 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature