ArticleOncotarget2018
STAT5 inhibition induces TRAIL/DR4 dependent apoptosis in peripheral T-cell lymphoma.
Article in Oncotarget, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
- The tumor suppressor NDRG2 recruits protein phosphatase 2A to suppress STAT5 phosphorylation in adult T-cell leukemia/lymphoma.The Journal of biological chemistry · 2026Article
- Review
- Recurrent Missense Driver STAT5BAnti-cancer agents in medicinal chemistry · 2025Article
- The JAK-STAT Signaling Pathway in Epilepsy.Current neuropharmacology · 2023Review
- Combined Inhibition of Bcl2 and Bcr-Abl1 Exercises Anti-Leukemia Activity but Does Not Eradicate the Primitive Leukemic Cells.Journal of clinical medicine · 2021Article
- rigrag: high-resolution mapping of genic targeting preferences during HIV-1 integration in vitro and in vivo.Nucleic acids research · 2021Article
- Primary Gastrointestinal T/NK Cell Lymphoma.Cancers · 2021Article
- Repurposing antipsychotics of the diphenylbutylpiperidine class for cancer therapy.Seminars in cancer biology · 2021Review
- Generation of pralatrexate resistant T-cell lymphoma lines reveals two patterns of acquired drug resistance that is overcome with epigenetic modifiers.Genes, chromosomes & cancer · 2020Article
- Whole-genome sequencing reveals potent therapeutic strategy for monomorphic epitheliotropic intestinal T-cell lymphoma.Blood advances · 2020Article
- Involvement of STAT5 in Oncogenesis.Biomedicines · 2020Review
- Phosphorylated STAT3 (Tyr705) as a biomarker of response to pimozide treatment in triple-negative breast cancer.Cancer biology & therapy · 2020Article
- Targeting the JAK/STAT Pathway in T Cell Lymphoproliferative Disorders.Current hematologic malignancy reports · 2019Review
- Nanoparticles Targeting STATs in Cancer Therapy.Cells · 2019Review
- BRD9 binds cell type-specific chromatin regions regulating leukemic cell survival via STAT5 inhibition.Cell death & disease · 2019Article
- Transcriptional Analysis of Lennert Lymphoma Reveals a Unique Profile and Identifies Novel Therapeutic Targets.Frontiers in genetics · 2019Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Peripheral T-cell lymphoma (PTCL) is a rare, aggressive, heterogeneous, Non-Hodgkin's lymphoma with poor prognosis and inadequate response to current therapies. Recent sequencing studies indicate a prevalence of activating mutations in the JAK/STAT signaling pathway. Oncogenic mutations in STAT5B, observed in approximately one third of cases of multiple different PTCL subtypes, correlate with inferior patient outcomes. Therefore, interest in the development of therapeutic strategies for targeting STAT5 in PTCL is warranted. In this study, we show that the drug pimozide inhibits STAT5 in PTCL, leading to apoptotic cell death by means of the TRAIL/DR4 dependent extrinsic apoptotic pathway. Pimozide induced PTCL cell death is caspase 8 dependent, increases the expression of the TRAIL receptor, DR4, on the surface of pre-apoptotic PTCL cells, and enhances TRAIL induced apoptosis in a TRAIL dependent manner. In parallel, we show that mRNA and protein levels of intrinsic pathway BCL-2 family members and mitochondrial membrane potential remain unaffected by STAT5 knockdown and/or inhibition. In primary PTCL patient samples, pimozide inhibits STAT5 activation and induces apoptosis. Our data support a role for STAT5 inhibition in PTCL and implicate potential utility for inhibition of STAT5 and activation of the extrinsic apoptotic pathway as combination therapy in PTCL.
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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.