PLZF/ZBTB16, a glucocorticoid response gene in acute lymphoblastic leukemia, interferes with glucocorticoid-induced apoptosis

https://doi.org/10.1016/j.jsbmb.2010.04.019Get rights and content
Under a Creative Commons license
open access

Abstract

Glucocorticoids (GCs) cause cell cycle arrest and apoptosis in lymphoid cells which is exploited to treat lymphoid malignancies. The mechanisms of these anti-leukemic GC effects are, however, poorly understood. We previously defined a list of GC-regulated genes by expression profiling in children with acute lymphoblastic leukemia (ALL) during systemic GC monotherapy and in experimental systems of GC-induced apoptosis. PLZF/ZBTB16, a transcriptional repressor, was one of the most promising candidates derived from this screen. To investigate its role in the anti-leukemic GC effects, we performed overexpression and knock-down experiments in CCRF-CEM childhood ALL cells. Transgenic PLZF/ZBTB16 alone had no detectable effect on cell proliferation or survival, but reduced sensitivity to GC-induced apoptosis but not apoptosis induced by antibodies against Fas/CD95 or 3 different chemotherapeutics. Knock-down of ZBTB16 entailed a small, but significant, increase in cell death induction by GC. Affymetrix Exon array-based whole genome expression profiling revealed that PLZF/ZBTB16 induction did not significantly alter the expression profile, however, it interfered with the regulation of numerous GC response genes, including BCL2L11/Bim, which has previously been shown to be responsible for cell death induction in CCRF-CEM cells. Thus, the protective effect of PLZF/ZBTB16 can be attributed to interference with transcriptional regulation by GC.

Keywords

Acute lymphoblastic leukemia
CCRF-CEM cell line
Exon array-based expression profiling
Functional gene analysis
Glucocorticoid-induced apoptosis
PLZF/ZBTB16

Cited by (0)

1

Present address: Institute of Biochemistry and Biotechnology, University of Veterinary and Animal Sciences, Lahore, Pakistan.