ArticleLeukemia2019
Dependency on the TYK2/STAT1/MCL1 axis in anaplastic large cell lymphoma.
Article in Leukemia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 28 papers.
What it found
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Who cites it
28 citing papers in PubMed, 54 citations in OpenAlex.
- Anti-Cancer Potential of a new Derivative of Caffeic Acid Phenethyl Ester targeting the Centrosome.Redox biology · 2025Article
- Mcm5 mutation leads to silencing of Stat1-bcl2 which accelerating apoptosis of immature T lymphocytes with DNA damage.Cell death & disease · 2025Article
- Advances in peripheral T cell lymphomas: pathogenesis, genetic landscapes and emerging therapeutic targets.Histopathology · 2025Review
- BIA-ALCL and BIA-SCC: Updates on Clinical Features and Genetic Mutations for Latest Recommendations.Medicina (Kaunas, Lithuania) · 2024Review
- STAT3 couples activated tyrosine kinase signaling to the oncogenic core transcriptional regulatory circuitry of anaplastic large cell lymphoma.Cell reports. Medicine · 2024Article
- Targeting CCR7-PI3Kγ overcomes resistance to tyrosine kinase inhibitors in ALK-rearranged lymphoma.Science translational medicine · 2023Article
- Oncogenic TYK2 P760L kinase is effectively targeted by combinatorial TYK2, mTOR and CDK4/6 kinase blockade.Haematologica · 2023Article
- Phosphorylated STAT3 as a potential diagnostic and predictive biomarker in ALKFrontiers in immunology · 2023Article
- PDGFRβ promotes oncogenic progression via STAT3/STAT5 hyperactivation in anaplastic large cell lymphoma.Molecular cancer · 2022Article
- Tyrosine phosphatases regulate resistance to ALK inhibitors in ALK+ anaplastic large cell lymphoma.Blood · 2022Article
- Inhibition of MCL1 induces apoptosis in anaplastic large cell lymphoma and in primary effusion lymphoma.Scientific reports · 2022Article
- Identification of Gene-Tyrosine Kinase 2 (TYK2) in Head and Neck Squamous Cell Carcinoma Patients-An Integrated Bioinformatics Approach.Disease markers · 2022Article
- Holistic View of ALK TKI Resistance in ALK-Positive Anaplastic Large Cell Lymphoma.Frontiers in oncology · 2022Review
- Review
- Super-enhancer-based identification of a BATF3/IL-2R-module reveals vulnerabilities in anaplastic large cell lymphoma.Nature communications · 2021Article
- Review
- Cirsiliol targets tyrosine kinase 2 to inhibit esophageal squamous cell carcinoma growth in vitro and in vivo.Journal of experimental & clinical cancer research : CR · 2021Article
- Janus Kinases in Leukemia.Cancers · 2021Review
- IL-22 Signaling in the Tumor Microenvironment.Advances in experimental medicine and biology · 2021Article
- Identification of Prognostic Biomarkers and Molecular Targets Among JAK Family in Breast Cancer.Journal of inflammation research · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
34 authors at 12 institutions in 6 countries.
Funding
Abstract
TYK2 is a member of the JAK family of tyrosine kinases that is involved in chromosomal translocation-induced fusion proteins found in anaplastic large cell lymphomas (ALCL) that lack rearrangements activating the anaplastic lymphoma kinase (ALK). Here we demonstrate that TYK2 is highly expressed in all cases of human ALCL, and that in a mouse model of NPM-ALK-induced lymphoma, genetic disruption of Tyk2 delays the onset of tumors and prolongs survival of the mice. Lymphomas in this model lacking Tyk2 have reduced STAT1 and STAT3 phosphorylation and reduced expression of Mcl1, a pro-survival member of the BCL2 family. These findings in mice are mirrored in human ALCL cell lines, in which TYK2 is activated by autocrine production of IL-10 and IL-22 and by interaction with specific receptors expressed by the cells. Activated TYK2 leads to STAT1 and STAT3 phosphorylation, activated expression of MCL1 and aberrant ALCL cell survival. Moreover, TYK2 inhibitors are able to induce apoptosis in ALCL cells, regardless of the presence or absence of an ALK-fusion. Thus, TYK2 is a dependency that is required for ALCL cell survival through activation of MCL1 expression. TYK2 represents an attractive drug target due to its essential enzymatic domain, and TYK2-specific inhibitors show promise as novel targeted inhibitors for ALCL.
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Registered trials
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.