ArticleThe Journal of investigative dermatology2021
Jak-STAT Inhibition Mediates Romidepsin and Mechlorethamine Synergism in Cutaneous T-Cell Lymphoma.
Article in The Journal of investigative dermatology, 2021. 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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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- Targeting FOXM1 regulates metabolic signatures through ROS-dependent JNK/Bmi1/Skp2 axis in human cutaneous T-cell lymphoma.Cell death & disease · 2026Article
- Real-world efficacy and safety of golidocitinib in 3 patients with relapsed/refractory peripheral T-cell lymphoma.Frontiers in oncology · 2026Article
- Treatment of Sezary syndrome with combination romidepsin and tofacitinib: A case report.JAAD case reports · 2025Article
- Epigenetics: Mechanisms, potential roles, and therapeutic strategies in cancer progression.Genes & diseases · 2024Review
- Cantharidin overcomes IL-2Rα signaling-mediated vorinostat resistance in cutaneous T-cell lymphoma through reactive oxygen species.Journal for immunotherapy of cancer · 2024Article
- Romidepsin and Afatinib Abrogate Jak-Signal Transducer and Activator of Transcription Signaling and Elicit Synergistic Antitumor Effects in Cutaneous T-Cell Lymphoma.The Journal of investigative dermatology · 2024Article
- RuBi-Ruxolitinib: A Photoreleasable Antitumor JAK Inhibitor.Journal of the American Chemical Society · 2024Article
- Article
- GATA-3-dependent Gene Transcription is Impaired upon HDAC Inhibition.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- "Next top" mouse models advancing CTCL research.Frontiers in cell and developmental biology · 2024Review
- Role of cytokine in malignant T-cell metabolism and subsequent alternation in T-cell tumor microenvironment.Frontiers in oncology · 2023Review
- Safety and Danger Considerations of Novel Treatments for Atopic Dermatitis in Context of Primary Cutaneous Lymphomas.International journal of molecular sciences · 2021Review
- Review
- Role of tumor microenvironment composition and metabolism in lymphoid malignancies and therapeutic strategies.Cell transplantationReview
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Sézary syndrome is an aggressive and disseminated form of cutaneous T-cell lymphoma associated with dismal prognosis in which the histone deacetylase inhibitor romidepsin has shown remarkable activity as a single agent. However, clinical responses to romidepsin are typically transient, highlighting the need for more effective therapies. In this study, we show synergistic antilymphoma effects of romidepsin in combination with mechlorethamine, an alkylating agent, in cutaneous T-cell lymphoma cell lines and primary samples with strong antitumor effects in an in vivo model of Sézary syndrome. Mechanistically, gene expression profiling points to abrogation of Jak/signal transducer and activator of transcription (STAT) signaling as an important mediator of this interaction. Consistently, the combination of mechlorethamine plus romidepsin resulted in downregulation of STAT5 phosphorylation in romidepsin-sensitive cell lines and primary Sézary syndrome samples, but not in romidepsin-resistant tumors. Moreover, in further support of Jak/STAT signaling as a modulator of romidepsin activity in cutaneous T-cell lymphoma, treatment with romidepsin in combination with Jak inhibitors resulted in markedly increased therapeutic responses. Overall, these results support a role for romidepsin plus mechlorethamine in combination in the treatment of cutaneous T-cell lymphoma and uncover a previously unrecognized role for Jak/STAT signaling in the response to romidepsin and romidepsin-based combination therapies in Sézary syndrome.
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Registered trials
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