ArticleEMBO molecular medicine2022
Blocking STAT3/5 through direct or upstream kinase targeting in leukemic cutaneous T-cell lymphoma.
Article in EMBO molecular medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 28 citations in OpenAlex.
- Cutaneous T Cell Lymphoma: Targeting the Survival Network in Mycosis Fungoides and Sézary Syndrome.Cancers · 2026Review
- STAT1/3/5 Functions Driving Lipid and Energy Metabolism in Cancer and Immunity.International journal of molecular sciences · 2026Review
- IQDMA disrupts STAT5 nuclear transport through CDC42-PAK2 axis collapse in cutaneous T-cell lymphoma.Frontiers in immunology · 2026Article
- Dynamics of checkpoint receptors in γδ T cell subsets are associated with clinical response during anti-PD-1 immunotherapies.EMBO molecular medicine · 2026Article
- Thrombopoietin increases susceptibility for EVI1 + KMT2A-MLLT3-driven AML expressing stem cell genes linked to poor outcome.Nature communications · 2025Article
- Dual STAT3/STAT5 inhibition as a novel treatment strategy in T-prolymphocytic leukemia.Leukemia · 2025Article
- The Role of the p21-Activated Kinase Family in Tumor Immunity.International journal of molecular sciences · 2025Review
- Dual specific STAT3/5 degraders effectively block acute myeloid leukemia and natural killer/T cell lymphoma.HemaSphere · 2024Article
- Article
- Hyperactive STAT5 hijacks T cell receptor signaling and drives immature T cell acute lymphoblastic leukemia.The Journal of clinical investigation · 2024Article
- Article
- Essential contribution of the JAK/STAT pathway to carcinogenesis, lytic infection of herpesviruses and pathogenesis of COVID‑19 (Review).Molecular medicine reports · 2024Review
- Specific Targeting of STAT3 in B Cells Suppresses Progression of B Cell Lymphoma.International journal of molecular sciences · 2023Article
- Blocking STAT3/5 through direct or upstream kinase targeting in leukemic cutaneous T-cell lymphoma.EMBO molecular medicine · 2022Article
Corrections and comments
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Authors and funding
46 authors at 10 institutions in 3 countries.
Funding
Abstract
Leukemic cutaneous T-cell lymphomas (L-CTCL) are lymphoproliferative disorders of skin-homing mature T-cells causing severe symptoms and high mortality through chronic inflammation, tissue destruction, and serious infections. Despite numerous genomic sequencing efforts, recurrent driver mutations have not been identified, but chromosomal losses and gains are frequent and dominant. We integrated genomic landscape analyses with innovative pharmacologic interference studies to identify key vulnerable nodes in L-CTCL. We detected copy number gains of loci containing the STAT3/5 oncogenes in 74% (n = 17/23) of L-CTCL, which correlated with the increased clonal T-cell count in the blood. Dual inhibition of STAT3/5 using small-molecule degraders and multi-kinase blockers abolished L-CTCL cell growth in vitro and ex vivo, whereby PAK kinase inhibition was specifically selective for L-CTCL patient cells carrying STAT3/5 gains. Importantly, the PAK inhibitor FRAx597 demonstrated encouraging anti-leukemic activity in vivo by inhibiting tumor growth and disease dissemination in intradermally xenografted mice. We conclude that STAT3/5 and PAK kinase interaction represents a new therapeutic node to be further explored in L-CTCL.
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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.