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| Status |
Public on Mar 18, 2013 |
| Title |
Gene expression profile of the human T-ALL cell line JURKAT after TYK2 and STAT1 knockdown |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Targeted molecular therapy has yielded remarkable outcomes in certain cancers, but specific therapeutic targets remain elusive for many others. As a result of two independent RNA interference (RNAi) screens, we identified pathway dependence on a member of the JAK tyrosine kinase family, TYK2, and its downstream effector STAT1 in T-cell acute lymphoblastic leukemia (T-ALL). Gene knockdown experiments consistently demonstrated TYK2 dependence in both T-ALL primary specimens and cell lines, and a small-molecule inhibitor of JAK kinase activity induced T-ALL cell death. Activation of this TYK2-STAT1 pathway in T-ALL cell lines occurs by gain-of-function TYK2 mutations or activation of IL-10 receptor signaling, and this pathway mediates T-ALL cell survival through upregulation of the anti-apoptotic protein BCL2. These findings indicate that in many T-ALL cases, the leukemic cells are dependent upon the TYK2-STAT1-BCL2 pathway for continued survival, supporting the development of molecular therapies targeting TYK2 and other components of this pathway.
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| Overall design |
Human T-ALL cell line JURKAT cells were transduced with TYK2 (TYK2#2 or #3), STAT1 (STAT1#2 or #3) or control shRNAs (GFP and Luc). Experiment was done in biological duplicate ("dup1" and "dup2") . A total of 12 RNA samples (4 control, 4 TYK2 knockdown and 4 STAT1 knockdown) were used for microarray gene expression analysis.
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| Contributor(s) |
Sanda T, Look AT |
| Citation(s) |
23471820 |
| Submission date |
Feb 25, 2013 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Takaomi Sanda |
| E-mail(s) |
takaomi_sanda@dfci.harvard.edu
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| Organization name |
Dana-Farber Cancer Institute
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| Street address |
450 Brookline Ave
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| City |
Boston |
| ZIP/Postal code |
02215 |
| Country |
USA |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA190703 |
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