ArrayExpress Uploader0humanshSTAT1shSTAT1shSTAT1shSTAT1shTYK2shTYK2shTYK2shTYK2shLucshLucshGFPshGFP2504arrayexpress_sid4Targeted molecular therapy has yielded remarkable outcomes in certain cancers, but specific therapeutic targets remain elusive for many...E-GEOD-44652/profile/8773/arrayexpressuploader112acute lymphoblastic leukemiacellleukemialinelymphoblastic leukemiaproteintyrosineDec.12, 2014Falsegene-expression-profile-of-the-human-t-all-cell-liE-GEOD-44652_A-AFFY-44Gene expression profile of the human T-ALL cell line JURKAT after TYK2 and STAT1 knockdownJul.12, 2014Targeted 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.http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-44652http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-44652/samples/