{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T08:06:59Z","timestamp":1788336419629,"version":"build-2803163510"},"reference-count":34,"publisher":"American Medical Association (AMA)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Dermatol"],"published-print":{"date-parts":[[2026,1,1]]},"abstract":"\n Importance<\/jats:title>\n T-cell receptor (TCR) clonotype patterns across disease stages and histologic subtypes in mycosis fungoides (MF) and S\u00e9zary syndrome (SS) remain poorly characterized, limiting their use in risk stratification.<\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n To assess the association of TCR \u03b2 (TCRB) and \u03b3 (TCRG) clonotypes with disease stage, folliculotropism, large-cell transformation, and overall survival (OS) as well as clonal abundance (percentage of total reads) with immune checkpoint expression.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This retrospective cohort study conducted at City of Hope (Duarte, California) included patients with stage IA to IVB MF\/SS who underwent TCR next-generation sequencing on lesional skin biopsy specimens collected between June 2020 to October 2024; duplicate samples were excluded. Analyses were performed from November 2024 to April 2025.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Associations between clinical and genetic categorical variables were evaluated using the Fisher exact test. OS was analyzed using Kaplan-Meier estimates, with univariate and multivariable models applied to assess prognostic factors.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Of the 125 patients (42 female [33.6%] and 74 male individuals [66.4%]; mean [SD] age, 62.4 [15.9] years) who underwent TCR sequencing, at least 1 clonal TCRB and\/or TCRG gene segment was identified in 98 patients (78%). Clonal TCRB and TCRG segments were detected in 72 (57.6%) and 92 patients (73.6%), respectively. The clonal Vb20 segment was significantly associated with folliculotropism and concurrent large-cell transformation compared with classic MF\/SS (7 of 17 [41%] vs 0 of 30 [0%];\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001), marginally significantly associated with advanced-stage MF\/SS compared with early-stage MF (8 of 38 [21%] vs 0 of 34 [0%];\n P<\/jats:italic>\n \u2009=\u2009.01). Clonal Vg8 was significantly associated with advanced-stage MF\/SS compared with early-stage MF (25 of 53 [47%] vs 8 of 39 [21%];\n P<\/jats:italic>\n \u2009=\u2009.01) and correlated with poorer OS. Additionally, the higher percentage of total reads for TCRG was positively correlated with increased expression of immune checkpoints programmed cell death 1 and inducible T-cell costimulator but not with programmed cell death ligand 1.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n This cohort study\u2019s analysis of TCRB and TCRG repertoires identified specific clonotypes that were associated with more aggressive subtypes and poorer survival in patients with MF\/SS. Incorporating TCR sequencing into clinical practice may enhance risk stratification, enabling earlier identification of high-risk patients who could benefit from closer monitoring and timely implementation of more intensive treatment strategies in the disease course to improve clinical outcomes.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamadermatol.2025.4081","type":"journal-article","created":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T15:31:09Z","timestamp":1761147069000},"page":"8","source":"Crossref","is-referenced-by-count":10,"title":["T-Cell Receptor Clonotypes and Aggressive Subtypes in Cutaneous T-Cell Lymphoma"],"prefix":"10.1001","volume":"162","author":[{"given":"Liliana L.","family":"Crisan","sequence":"first","affiliation":[{"name":"Division of Dermatology, City of Hope Comprehensive Cancer Center and Beckman Research Institute, Duarte, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanpeng J.","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, Department of Computational and Quantitative Medicine, City of Hope Comprehensive Cancer Center and Beckman Research Institute, Duarte, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Afkhami","sequence":"additional","affiliation":[{"name":"Department of Pathology, City of Hope Comprehensive Cancer Center and Beckman Research Institute, Duarte, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmine","family":"Zain","sequence":"additional","affiliation":[{"name":"Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Comprehensive Cancer Center and Beckman Research Institute, Duarte, California"},{"name":"Division of Hematology\/Oncology, Memorial Sloan Kettering Cancer Center, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven T.","family":"Rosen","sequence":"additional","affiliation":[{"name":"Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Comprehensive Cancer Center and Beckman Research Institute, Duarte, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raju","family":"Pillai","sequence":"additional","affiliation":[{"name":"Department of Pathology, City of Hope Comprehensive Cancer Center and Beckman Research Institute, Duarte, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"Querfeld","sequence":"additional","affiliation":[{"name":"Division of Dermatology, City of Hope Comprehensive Cancer Center and Beckman Research Institute, Duarte, California"},{"name":"Department of Pathology, City of Hope Comprehensive Cancer Center and Beckman Research Institute, Duarte, California"},{"name":"Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Comprehensive Cancer Center and Beckman 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