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Series GSE10283 Query DataSets for GSE10283
Status Public on Feb 01, 2008
Title BCR/ABL1-Dependent Transcriptional Response Reveals Enrichment for Genes Involved in Negative Feedback Regulation
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Philadelphia (Ph) chromosome-positive leukemia is characterized by the BCR/ABL1 fusion protein that affects a wide range of signal transduction pathways. The knowledge about its downstream target genes is, however, still quite limited. To identify novel BCR/ABL1-regulated genes we used global gene expression profiling of several Ph-positive and Ph-negative cell lines treated with imatinib. Following imatinib treatment, the Ph-positive cells showed decreased growth, viability, and reduced phosphorylation of BCR/ABL1 and STAT5. In total, 142 genes were identified as being dependent on BCR/ABL1-mediated signaling, mainly including genes involved in signal transduction, e.g. the JAK/STAT, MAPK, TGFB and insulin signaling pathways, and in regulation of metabolism. Interestingly, BCR/ABL1 was found to activate several genes involved in negative feedback regulation (CISH, SOCS2, SOCS3, PIM1, DUSP6, and TNFAIP3), which may act to indirectly suppress the tumor promoting effects exerted by BCR/ABL1. In addition, several genes identified as deregulated upon BCR/ABL1 expression could be assigned to the TGFB and NFkB signaling pathways, as well as to reflect the metabolic adjustments needed for rapidly growing cells. Apart from providing important pathogenetic insights into BCR/ABL1-mediated leukemogenesis, the present study also provides a number of pathways/individual genes that may provide attractive targets for future development of targeted therapies.
Keywords: global gene expression profiling, Ph chromosome, BCR/ABL1, imatinib mesylate
 
Overall design Five Philadelphia-positive (Ph+) and five Philadelphia-negative (Ph-) cell lines were cultured in the absence or presence of 1 microM imatinib mesylate for 3 and 12 hours. Total RNA was extracted from untreated and treated cell cultures at both time points, resulting in 4 samples per cell line. RNA extraction, labeling, hybridization, washing, scanning, and feature analysis were performed as described (Håkansson et al., 2008, Genes Chromosomes Cancer). Dye-swap labeling was performed in 32 out of 40 samples. In total, 72 slides were hybridized and scanned. The transcriptional response was studied using the mean value of the 3 and 12 hour microarray measurements.
 
Contributor(s) Håkansson P, Nilsson B, Andersson A, Lassen C, Gullberg U, Fioretos T
Citation(s) 18181176
Submission date Jan 25, 2008
Last update date Mar 19, 2012
Contact name Petra Johnels
E-mail(s) petra.johnels@med.lu.se, thoas.fioretos@med.lu.se
Phone +46 46 173398
Fax +46 46 131061
Organization name Lund University
Department Clinical Genetics
Street address Lund University Hospital
City Lund
ZIP/Postal code 221 85
Country Sweden
 
Platforms (1)
GPL4861 Swegene Human 27K RAP (positions from file)
Samples (72)
GSM259661 K562_untreated_3h_technical replicate 1
GSM259662 K562_untreated_12h_technical replicate 1
GSM259663 K562_+IM_3h_technical replicate 1
Relations
BioProject PRJNA108487

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE10283_RAW.tar 168.0 Mb (http)(custom) TAR (of GPR)
Processed data included within Sample table
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