title: Sezary syndrome and mycosis fungoides arise from distinct T-cell subsets: a biologic rationale for their distinct clinical behaviors.
abstract: Cutaneous T-cell lymphoma (CTCL) encompasses leukemic variants (L-CTCL) such as Sézary syndrome (SS) and primarily cutaneous variants such as mycosis fungoides (MF). To clarify the relationship between these clinically disparate presentations, we studied the phenotype of T cells from L-CTCL and MF. Clonal malignant T cells from the blood of L-CTCL patients universally coexpressed the lymph node homing molecules CCR7 and L-selectin as well as the differentiation marker CD27, a phenotype consistent with central memory T cells. CCR4 was also universally expressed at high levels, and there was variable expression of other skin addressins (CCR6, CCR10, and CLA). In contrast, T cells isolated from MF skin lesions lacked CCR7/L-selectin and CD27 but strongly expressed CCR4 and CLA, a phenotype suggestive of skin resident effector memory T cells. Our results suggest that SS is a malignancy of central memory T cells and MF is a malignancy of skin resident effector memory T cells.
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital/Harvard, Boston, MA, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Campbell
authors.forename: Rachael A
authors.initials: RA
authors.lastname: Clark
authors.forename: Rei
authors.initials: R
authors.lastname: Watanabe
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Kupper
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000473:pathology*; D054421:Chemokine CCL21 / Q000494:pharmacology; D054422:Chemokine CCL22 / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006801:Humans; D007156:Immunologic Memory; D019041:L-Selectin / Q000096:biosynthesis / Q000235:genetics; D008198:Lymph Nodes / Q000276:immunology; D009182:Mycosis Fungoides / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000737:chemistry / Q000473:pathology; D010641:Phenotype; D054400:Receptors, CCR7 / Q000096:biosynthesis / Q000235:genetics; D012751:Sezary Syndrome / Q000473:pathology*; D012867:Skin / Q000166:cytology / Q000276:immunology; D012878:Skin Neoplasms / Q000473:pathology*; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000473:pathology*
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; C515370:CCR7 protein, human; D054421:Chemokine CCL21; D054422:Chemokine CCL22; D054400:Receptors, CCR7; D019041:L-Selectin