Transcriptomics

Dataset Information

0

Anti-leukemic effects of glucocorticoids in childhood acute lymphoblastic leukemia: conserved transcriptional pathway to cell cycle arrest but not to cell death


ABSTRACT: Glucocorticoids (GCs) cause cell cycle arrest and cell death in malignant lymphoblasts and constitute a principal component in the treatment of childhood acute lymphoblastic leukemia (chALL). To address the molecular mechanism of the anti-leukemic GC effects, we performed microarray-based whole-genome expression profiling of lymphoblasts from 46 patients undergoing systemic GC mono-therapy and combined these data with clinical information (e.g., molecular genotype, reduction in peripheral blood lymphoblasts, GC bioactivity in the patient's blood) using differential gene expression with GO analyses, regression modeling correlating transcriptional with clinical response, and an iterative elastic net approach to address combinatorial effects of gene expression and regulation. Our analysis revealed that, although there are a number of common response genes, the transcriptional response to GC in vivo varies considerably in the different molecular subtypes of this disease. Regarding the anti-leukemic response, repression of mRNA for key regulators of G2/M transition was commonly observed in all subtypes whereas we failed to observe a common transcriptional control of apoptosis genes. Although sets of genes were identified which in combination appear to contribute to the apoptotic response, the data as a whole suggest that GC-induced cell death does not result from conserved transcriptional regulation of the apoptotic machinery itself but might rather result from a wide spread deregulation of gene expression.

ORGANISM(S): Homo sapiens

PROVIDER: GSE73578 | GEO | 2017/09/22

SECONDARY ACCESSION(S): PRJNA297359

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2010-05-07 | GSE15820 | GEO
2015-05-07 | GSE65872 | GEO
2015-05-07 | E-GEOD-65872 | biostudies-arrayexpress
2013-09-17 | E-GEOD-42221 | biostudies-arrayexpress
2013-09-17 | GSE42221 | GEO
2009-08-16 | E-GEOD-17195 | biostudies-arrayexpress
2022-03-11 | PXD025232 | Pride
2022-03-11 | PXD025271 | Pride
2022-03-11 | PXD025230 | Pride
2022-03-11 | PXD025228 | Pride