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Title: PRAME induced inhibition of retinoic acid receptor signaling-mediated differentiation - a possible target for ATRA response in AML without t(15;17)      
availability:
available
aggregation:
instance of dataset
privacy:
not applicable
refinement:
curated
dateReleased:
06-02-2014
ID:
E-GEOD-43258
description:
Purpose: In acute myeloid leukemia (AML) without retinoic acid receptor (RAR) rearrangement the effect of all-trans retinoic acid (ATRA) is still poorly understood despite an association of NPM1 mutation and ATRA response. Recently, PRAME (preferentially expressed antigen in melanoma) has been shown to be a dominant repressor of RAR-signaling. Experimental design: Thus, we further investigated ATRA response mechanisms, especially the impact of PRAME expression on ATRA-responsiveness by profiling gene expression in K562 cell lines. Results: Our data revealed a PRAME-expression associated gene pattern to be significantly enriched for genes involved in the retinoic acid metabolic process. In leukemia cell line models we could demonstrate that retinoic acid-regulated cell proliferation and differentiation are impacted by PRAME expression. Conclusions: PRAME seems to impair differentiation and to increase proliferation likely via blocking RAR-signaling, which might be reversed by ATRA. For the cell line model GEP was performed using Affymetrix Human Genome U133plus2.0 Array technology according to the manufacturer’s recommendations as previously reported. siRNA and scrRNA treated as well as ATRA treated K562 cells stemming from independent experiments were profiled. Using the BRB Array Tools software package fluorescence ratios were normalized by applying the RMA algorithm and supervised ClassComparison PathwayClassComparison analyses were performed.
keywords:
transcription profiling by array
format:
HTML
storedIn:
Array Express
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not compressed
accessType:
landing page
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primary:
true
accessURL: https://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-43258
format:
JSON
storedIn:
OmicsDI
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not compressed
accessType:
download
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none
authentication:
none
primary:
false
accessURL: www.omicsdi.org/ws/dataset/arrayexpress-repository/E-GEOD-43258.json
format:
XML
storedIn:
OmicsDI
qualifier:
not compressed
accessType:
download
authorization:
none
authentication:
none
primary:
false
accessURL: http://www.omicsdi.org/ws/dataset/arrayexpress-repository/E-GEOD-43258.xml
ID:
SCR:014747
name:
Omics Discovery Index
abbreviation:
OmicsDI
homePage: http://www.omicsdi.org/