|
| 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 |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| 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)
|
|
| Relations |
| BioProject |
PRJNA283116 |
Less...
More...