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Schlafen 11 (SLFN11) has emerged as a key determinant of sensitivity to DNA-damaging agents, yet its role in CTCL remains unclear. Here, we examined SLFN11 expression in two major CTCL subtypes\u2014mycosis fungoides (MF) and S\u00e9zary syndrome (SS). Immunohistochemistry revealed SLFN11 positivity in 52% of MF (13\/25) and 80% of SS (4\/5) cases, with multivariate analysis showing a significant correlation between SLFN11 and CD30 expression. In normal human peripheral blood mononuclear cells, CD3\/CD28\/IL-2 stimulation induced co-expression of SLFN11 and CD30 in T cells, which was accompanied by heightened sensitivity to DNA-damaging agents. The JAK inhibitor cerdulatinib suppressed both markers. Among five CTCL cell lines, HUT78\u2014expressing the highest SLFN11 levels\u2014was the most sensitive to DNA-damaging agents, whereas SLFN11 knockout conferred resistance. Attempts to restore SLFN11 expression in SLFN11-low CTCL cells using six (pre)clinical HDAC inhibitors produced inconsistent results across cell lines and drugs. Together, these findings identify SLFN11 and CD30 as co-expressed therapeutic targets in CTCL\u00a0and support the rationale for CD30-directed antibody\u2013DNA-damaging agent conjugates as a precision treatment strategy.<\/jats:p>","DOI":"10.1093\/narcan\/zcaf037","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T10:24:44Z","timestamp":1759832684000},"source":"Crossref","is-referenced-by-count":2,"title":["Co-expression of CD30 and SLFN11 serves as a dual biomarker for the treatment of cutaneous T-cell lymphoma"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0369-869X","authenticated-orcid":false,"given":"Takatoshi","family":"Shimauchi","sequence":"first","affiliation":[{"name":"Hamamatsu University School of Medicine Department of Dermatology, , Hamamatsu ,\u00a0431-3192,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junko","family":"Murai","sequence":"additional","affiliation":[{"name":"Division of Cell Growth and Tumor Regulation, Proteo-Science Center , Toon , Ehime , 791-0295,","place":["Japan"]},{"name":"Ehime University Graduate School of Medicine Department of Biochemistry and Molecular Genetics, , Toon , Ehime , 791-0295,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manami","family":"Iwasaki","sequence":"additional","affiliation":[{"name":"Hamamatsu University School of Medicine Department of Dermatology, , Hamamatsu ,\u00a0431-3192,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pawit","family":"Phadungsaksawasdi","sequence":"additional","affiliation":[{"name":"Hamamatsu University School of Medicine Department of Dermatology, , Hamamatsu ,\u00a0431-3192,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiyuki","family":"Ojima","sequence":"additional","affiliation":[{"name":"Hamamatsu University School of Medicine Department of Community Health and Preventive Medicine, , Hamamatsu , 431-3192","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuyasu","family":"Fujii","sequence":"additional","affiliation":[{"name":"Kindai University Hospital Department of Dermatology, , Osaka , 589-8511,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuya","family":"Honda","sequence":"additional","affiliation":[{"name":"Hamamatsu University School of Medicine Department of Dermatology, , Hamamatsu ,\u00a0431-3192,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,10,7]]},"reference":[{"key":"2025100706243782100_B1","volume-title":"WHO Classification of 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