Gene expression profile of the human T-ALL cell line JURKAT after TYK2 and STAT1 knockdown
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ABSTRACT: 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. 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.
ORGANISM(S): Homo sapiens
SUBMITTER: Takaomi Sanda
PROVIDER: E-GEOD-44652 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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