{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T08:06:51Z","timestamp":1788336411822,"version":"build-2803163510"},"reference-count":87,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T00:00:00Z","timestamp":1752710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NCI","award":["R01 CA132098"],"award-info":[{"award-number":["R01 CA132098"]}]},{"name":"NCI","award":["P30 CA010815"],"award-info":[{"award-number":["P30 CA010815"]}]},{"name":"NCI","award":["R50 CA211199"],"award-info":[{"award-number":["R50 CA211199"]}]},{"name":"NCI","award":["R01 CA122569"],"award-info":[{"award-number":["R01 CA122569"]}]},{"name":"Cancer Center","award":["R01 CA132098"],"award-info":[{"award-number":["R01 CA132098"]}]},{"name":"Cancer Center","award":["P30 CA010815"],"award-info":[{"award-number":["P30 CA010815"]}]},{"name":"Cancer Center","award":["R50 CA211199"],"award-info":[{"award-number":["R50 CA211199"]}]},{"name":"Cancer Center","award":["R01 CA122569"],"award-info":[{"award-number":["R01 CA122569"]}]},{"name":"Leukemia and Lymphoma Society","award":["R01 CA132098"],"award-info":[{"award-number":["R01 CA132098"]}]},{"name":"Leukemia and Lymphoma Society","award":["P30 CA010815"],"award-info":[{"award-number":["P30 CA010815"]}]},{"name":"Leukemia and Lymphoma Society","award":["R50 CA211199"],"award-info":[{"award-number":["R50 CA211199"]}]},{"name":"Leukemia and Lymphoma Society","award":["R01 CA122569"],"award-info":[{"award-number":["R01 CA122569"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: We examined the in vivo effects of successive treatments with the histone deacetylase (HDAC) inhibitor romidepsin in patients with cutaneous T-cell lymphoma (CTCL), using changes in gene expression in peripheral blood mononuclear cells (PBMCs). Methods: Exploiting data from a highly responsive CTCL patient through 12 months of treatment, we identified a malignant cell predictor (MCP), a gene signature associated with the diminishing numbers of circulating malignant cells. Results: The MCP was successfully validated in the patient\u2019s relapse sample 9 months after treatment was terminated and via an independent set of CTCL patient samples. Conclusions: The MCP set of genes contained novel CTCL markers, including membrane-associated proteins not normally expressed in lymphocytes. A subclass of those markers was also detectable in residual malignant cells undetected by flow cytometry in remission samples from a patient who relapsed 10 months later. We identified a subset of transcriptional regulators, miRNAs and methylation patterns associated with the effect of progressive treatments revealing potential mechanisms of transcriptional dysregulation and functional effects in the malignant cells. We demonstrate a role for transcriptional activator HLF, over-expressed in malignant cells, and downregulated transcriptional-suppressor and immune-modulator NFIL3, as regulators of CTCL-specific genes.<\/jats:p>","DOI":"10.3390\/cancers17142380","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T13:00:51Z","timestamp":1752757251000},"page":"2380","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cutaneous T-Cell Lymphoma: Yin-Yang Effects of Transcription Factors HLF and NFIL3 in Regulation of Malignant T-Cell Markers in the Context of HDAC Inhibitor Romidepsin Treatment"],"prefix":"10.3390","volume":"17","author":[{"given":"Andrew V.","family":"Kossenkov","sequence":"first","affiliation":[{"name":"The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2983-3893","authenticated-orcid":false,"given":"Noor","family":"Dawany","sequence":"additional","affiliation":[{"name":"The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9046-8799","authenticated-orcid":false,"given":"Sonali","family":"Majumdar","sequence":"additional","affiliation":[{"name":"The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia","family":"Chang","sequence":"additional","affiliation":[{"name":"The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Calen","family":"Nichols","sequence":"additional","affiliation":[{"name":"The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Wysocka","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3591-7893","authenticated-orcid":false,"given":"Richard","family":"Piekarz","sequence":"additional","affiliation":[{"name":"Cancer Therapy Evaluation Program, National Cancer Institute, Rockville, MD 20850, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael K.","family":"Showe","sequence":"additional","affiliation":[{"name":"The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan E.","family":"Bates","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology, Columbia University Irving Medical Center, New York, NY 10032, USA"},{"name":"Department of Hematology\/Oncology, James J. Peters VA Medical Center, Bronx, NY 10468, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain H.","family":"Rook","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen J.","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7818-4220","authenticated-orcid":false,"given":"Louise C.","family":"Showe","sequence":"additional","affiliation":[{"name":"The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,17]]},"reference":[{"key":"ref_1","first-page":"927","article-title":"Cutaneous Lymphoma of the Sezary and Bouvrain Type. 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