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Series GSE68562 Query DataSets for GSE68562
Status Public on Oct 31, 2015
Title Effect of a JAK inhibitor on gene expression of HUT78 cell line
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Developing targeted therapy for cutaneous T cell lymphoma (CTCL) patients still requires actionable mutated genes and deregulated pathways to be identified. There is increasing evidence that activating mutations in JAK genes and deregulated JAK/STAT signaling are important mechanisms involved in multiple B and T cell malignancies, including CTCL. Therefore, in this study we focused on studying the mutational status of JAK1, JAK2 and JAK3 genes in a series of human CTCL lesions and cell lines using next-generation sequencing (NGS). We found that 7 of 48 (14.7%) of the analyzed cases harbored mutations in the JAK1 and JAK3 genes that mainly affected the pseudokinase domain of the corresponding proteins. On the basis of these results, we used a specific JAK inhibitor (INCB018424) in a series of CTCL cell lines with deregulated JAK/STAT activity. Treatment of CTCL cells with INCB018424 resulted in dose-dependent reduction of activated STAT expression, diminished cell viability, and increased apoptosis. We also studied global changes in gene expression in cells with mutated JAK1 and JAK3 proteins treated with INCB018424 and identified multiple genes that were differentially regulated by JAK/STAT signaling, such as FGF20 (upregulated) and EGR1 (downregulated). Thus, our results show that the detection of deregulated JAK/STAT signaling in CTCL lesions via JAK mutations or other surrogate markers may serve to indicate the clinical use of JAK/STAT inhibitors.
Overall design 3 replicates of cells treated with DMSO or JAKi during 30 min and 3h
Contributor(s) Martinez N
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Submission date May 05, 2015
Last update date Nov 27, 2018
Contact name Nerea Martinez
Organization name IDIVAL
Lab Cancer Genomics
Street address Avda Cardenal Herrera Oria
City Santander
ZIP/Postal code E 39011
Country Spain
Platforms (2)
GPL13607 Agilent-028004 SurePrint G3 Human GE 8x60K Microarray (Feature Number version)
GPL16699 Agilent-039494 SurePrint G3 Human GE v2 8x60K Microarray 039381 (Feature Number version)
Samples (9)
GSM1675612 HUT78_control_rep1
GSM1675613 HUT78_JAKi_30min_rep1
GSM1675614 HUT78_JAKi_3h_rep1
BioProject PRJNA283116

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
GSE68562_Normalized_data_samples1-3_with_probename.txt.gz 1.3 Mb (ftp)(http) TXT
GSE68562_Normalized_data_samples4-9_with_probename.txt.gz 2.2 Mb (ftp)(http) TXT
GSE68562_RAW.tar 57.0 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table
Processed data are available on Series record

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