ArticleCancer discovery2013
TYK2-STAT1-BCL2 pathway dependence in T-cell acute lymphoblastic leukemia.
Article in Cancer discovery, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
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Who cites it
96 citing papers in PubMed, 143 citations in OpenAlex.
- Trial
- Vitamin D Deficiency in Leukemia: Implications for Pathophysiology, Treatment, and Supportive Care.Nutrients · 2026Review
- Therapeutic activation of PPARα contributes to NOTCH1 inhibition in T-cell acute lymphoblastic leukemia.BMC medicine · 2026Article
- Deep mutational scanning reveals pharmacologically relevant insights into TYK2 signaling and disease.eLife · 2026Article
- HDAC3 inhibition as a therapeutic strategy in T-cell acute lymphoblastic leukemia via the TYK2-STAT1-BCL2 signaling pathway.Frontiers in immunology · 2026Article
- Targeting the IKZF1/BCL-2 axis as a novel therapeutic strategy for treating acute T-cell lymphoblastic leukemia.Cancer biology & therapy · 2025Article
- Review of Promising Off-Label Use of Deucravacitinib.International journal of molecular sciences · 2025Review
- Cancer-associated fibroblasts shape the formation of budding cancer cells at the invasive front of human colorectal cancer.Communications biology · 2025Article
- Malignant JAK-signaling: at the interface of inflammation and malignant transformation.Leukemia · 2025Review
- Mcm5 mutation leads to silencing of Stat1-bcl2 which accelerating apoptosis of immature T lymphocytes with DNA damage.Cell death & disease · 2025Article
- CDK8/19 inhibition triggers a switch from mitosis to endomitosis in cord blood megakaryocytes.British journal of haematology · 2024Article
- MEK Inhibition Synergizes with TYK2 Inhibitors in NF1-Associated Malignant Peripheral Nerve Sheath Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Oncogenic TYK2 P760L kinase is effectively targeted by combinatorial TYK2, mTOR and CDK4/6 kinase blockade.Haematologica · 2023Article
- Venetoclax-Resistant T-ALL Cells Display Distinct Cancer Stem Cell Signatures and Enrichment of Cytokine Signaling.International journal of molecular sciences · 2023Article
- Heat-Shock Proteins in Leukemia and Lymphoma: Multitargets for Innovative Therapeutic Approaches.Cancers · 2023Review
- Therapeutic Targeting of MERTK and BCL-2 in T-Cell and Early T-Precursor Acute Lymphoblastic Leukemia.Cancers · 2022Article
- The expression and the tumor suppressor role of CLDN6 in colon cancer.Molecular and cellular biochemistry · 2022Article
- Exploring the oncogenic and therapeutic target potential of the MYB-TYK2 fusion gene in B-cell acute lymphoblastic leukemia.Cancer gene therapy · 2022Article
- JAK3 mutations and mitochondrial apoptosis resistance in T-cell acute lymphoblastic leukemia.Leukemia · 2022Article
- IPO11 regulates the nuclear import of BZW1/2 and is necessary for AML cells and stem cells.Leukemia · 2022Article
36 more citing papers are in PubMed but not listed here.
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Authors and funding
25 authors at 4 institutions in 1 country.
Funding
Abstract
unlabelledTargeted 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 Janus-activated kinase (JAK) tyrosine kinase family, TYK2, and its downstream effector STAT1, in T-cell acute lymphoblastic leukemia (T-ALL). Gene knockdown experiments consistently showed TYK2 dependence in both T-ALL primary specimens and cell lines, and a small-molecule inhibitor of JAK 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 interleukin (IL)-10 receptor signaling, and this pathway mediates T-ALL cell survival through upregulation of the antiapoptotic 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. SIGNIFICANCE: In recent years, "pathway dependence" has been revealed in specific types of human cancer, which can be important because they pinpoint proteins that are particularly vulnerable to antitumor-targeted inhibition (so-called Achilles’ heel proteins). Here, we use RNAi technology to identify a novel oncogenic pathway that involves aberrant activation of the TYK2 tyrosine kinase and its downstream substrate, STAT1, which ultimately promotes T-ALL cell survival through the upregulation of BCL2 expression
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.