Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of human blood lymphoblasts purified at three time points from childhood ALL samples (0h, 6-8h, 24h after treatment with prednisolone


ABSTRACT: Glucocorticoids (GC) are in most chemotherapy protocols for lymphoid malignancies, particularly childhood acute lymphoblastic leukaemia (ALL) for their ability to induce apoptosis in malignant blast. The underlying mechanism, however, has so far only been investigated in model systems. This study comprises Affymetrix hgu133 plus 2.0 analyses of; Peripheral blood lymphoblasts purified at three time points (0h, 6-8h, 24h after treatment initiation) from 13 children under therapy for ALL . Treated samples were compared to untreated (0h). For comparison, expression profiles were generated from an adult ALL patient, peripheral blood lymphocytes from GC-exposed healthy donors, GC-sensitive and -resistant ALL cell lines and mouse thymocytes treated with GC in vivo and in vitro. This second series comprises the additional samples mentioned above. Findings. An essentially complete list of GC-regulated candidate genes in clinical settings experimental and was generated, enabling immediate analysis of any gene with respect to its potential significance for GC-induced apoptosis in these systems. Gene regulations previously thought responsible for cell death in experimental systems were reconfirmed in few children only. In contrast, a small number of genes, most not implicated in GC-induced apoptosis previously, were co-ordinately regulated in the majority of children. Experiment Overall Design: replicates: prednisolone treated GSM60594, GSM60595. untreated: GSM60597, GSM60599. Bone marrow samples sorted / unsorted: GSM60601, GSM60603. Experiment Overall Design: Samples are assigned to various subgroups: sensitive systems, resistant systems, Prednisolone treated, ethanol (control) treated, cyclohexamide treated, untreated, 6 hours treatment and 24 hours treated. Experiment Overall Design: Glucocorticoid treated samples of patients or cell lines or healthy donors were compared to their untreated or ethanol treated counterparts.

ORGANISM(S): Homo sapiens

SUBMITTER: Johannes Rainer 

PROVIDER: E-GEOD-2842 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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The ability of glucocorticoids (GCs) to kill lymphoid cells led to their inclusion in essentially all chemotherapy protocols for lymphoid malignancies, particularly childhood acute lymphoblastic leukemia (ALL). GCs mediate apoptosis via their cognate receptor and subsequent alterations in gene expression. Previous investigations, including expression profiling studies with subgenome microarrays in model systems, have led to a number of attractive, but conflicting, hypotheses that have never been  ...[more]

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