Cargando…

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

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 wi...

Descripción completa

Detalles Bibliográficos
Autores principales: Wasim, Muhammad, Carlet, Michela, Mansha, Muhammad, Greil, Richard, Ploner, Christian, Trockenbacher, Alexander, Rainer, Johannes, Kofler, Reinhard
Formato: Texto
Lenguaje:English
Publicado: Pergamon 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2892747/
https://www.ncbi.nlm.nih.gov/pubmed/20435142
http://dx.doi.org/10.1016/j.jsbmb.2010.04.019
_version_ 1782182983622459392
author Wasim, Muhammad
Carlet, Michela
Mansha, Muhammad
Greil, Richard
Ploner, Christian
Trockenbacher, Alexander
Rainer, Johannes
Kofler, Reinhard
author_facet Wasim, Muhammad
Carlet, Michela
Mansha, Muhammad
Greil, Richard
Ploner, Christian
Trockenbacher, Alexander
Rainer, Johannes
Kofler, Reinhard
author_sort Wasim, Muhammad
collection PubMed
description 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.
format Text
id pubmed-2892747
institution National Center for Biotechnology Information
language English
publishDate 2010
publisher Pergamon
record_format MEDLINE/PubMed
spelling pubmed-28927472010-07-15 PLZF/ZBTB16, a glucocorticoid response gene in acute lymphoblastic leukemia, interferes with glucocorticoid-induced apoptosis Wasim, Muhammad Carlet, Michela Mansha, Muhammad Greil, Richard Ploner, Christian Trockenbacher, Alexander Rainer, Johannes Kofler, Reinhard J Steroid Biochem Mol Biol Article 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. Pergamon 2010-06 /pmc/articles/PMC2892747/ /pubmed/20435142 http://dx.doi.org/10.1016/j.jsbmb.2010.04.019 Text en © 2010 Elsevier Ltd. https://creativecommons.org/licenses/by-nc-nd/3.0/ Open Access under CC BY-NC-ND 3.0 (https://creativecommons.org/licenses/by-nc-nd/3.0/) license
spellingShingle Article
Wasim, Muhammad
Carlet, Michela
Mansha, Muhammad
Greil, Richard
Ploner, Christian
Trockenbacher, Alexander
Rainer, Johannes
Kofler, Reinhard
PLZF/ZBTB16, a glucocorticoid response gene in acute lymphoblastic leukemia, interferes with glucocorticoid-induced apoptosis
title PLZF/ZBTB16, a glucocorticoid response gene in acute lymphoblastic leukemia, interferes with glucocorticoid-induced apoptosis
title_full PLZF/ZBTB16, a glucocorticoid response gene in acute lymphoblastic leukemia, interferes with glucocorticoid-induced apoptosis
title_fullStr PLZF/ZBTB16, a glucocorticoid response gene in acute lymphoblastic leukemia, interferes with glucocorticoid-induced apoptosis
title_full_unstemmed PLZF/ZBTB16, a glucocorticoid response gene in acute lymphoblastic leukemia, interferes with glucocorticoid-induced apoptosis
title_short PLZF/ZBTB16, a glucocorticoid response gene in acute lymphoblastic leukemia, interferes with glucocorticoid-induced apoptosis
title_sort plzf/zbtb16, a glucocorticoid response gene in acute lymphoblastic leukemia, interferes with glucocorticoid-induced apoptosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2892747/
https://www.ncbi.nlm.nih.gov/pubmed/20435142
http://dx.doi.org/10.1016/j.jsbmb.2010.04.019
work_keys_str_mv AT wasimmuhammad plzfzbtb16aglucocorticoidresponsegeneinacutelymphoblasticleukemiainterfereswithglucocorticoidinducedapoptosis
AT carletmichela plzfzbtb16aglucocorticoidresponsegeneinacutelymphoblasticleukemiainterfereswithglucocorticoidinducedapoptosis
AT manshamuhammad plzfzbtb16aglucocorticoidresponsegeneinacutelymphoblasticleukemiainterfereswithglucocorticoidinducedapoptosis
AT greilrichard plzfzbtb16aglucocorticoidresponsegeneinacutelymphoblasticleukemiainterfereswithglucocorticoidinducedapoptosis
AT plonerchristian plzfzbtb16aglucocorticoidresponsegeneinacutelymphoblasticleukemiainterfereswithglucocorticoidinducedapoptosis
AT trockenbacheralexander plzfzbtb16aglucocorticoidresponsegeneinacutelymphoblasticleukemiainterfereswithglucocorticoidinducedapoptosis
AT rainerjohannes plzfzbtb16aglucocorticoidresponsegeneinacutelymphoblasticleukemiainterfereswithglucocorticoidinducedapoptosis
AT koflerreinhard plzfzbtb16aglucocorticoidresponsegeneinacutelymphoblasticleukemiainterfereswithglucocorticoidinducedapoptosis