title: High-scatter T cells: a reliable biomarker for malignant T cells in cutaneous T-cell lymphoma.
abstract: In early-stage cutaneous T-cell lymphoma (CTCL), malignant T cells are confined to skin and are difficult to isolate and discriminate from benign reactive cells. We found that T cells from CTCL skin lesions contained a population of large, high-scatter, activated skin homing T cells not observed in other inflammatory skin diseases. High-scatter T (T(HS)) cells were CD4(+) in CD4(+) mycosis fungoides (MF), CD8(+) in CD8(+) MF, and contained only clonal T cells in patients with identifiable malignant Vβ clones. T(HS) cells were present in the blood of patients with leukemic CTCL, absent in patients without blood involvement, and contained only clonal malignant T cells. The presence of clonal T(HS) cells correlated with skin disease in patients followed longitudinally. Clonal T(HS) cells underwent apoptosis in patients clearing on extracorporeal photopheresis but persisted in nonresponsive patients. Benign clonal T-cell proliferations mapped to the normal low-scatter T-cell population. Thus, the malignant T cells in both MF and leukemic CTCL can be conclusively identified by a unique scatter profile. This observation will allow selective study of malignant T cells, can be used to discriminate patients with MF from patients with other inflammatory skin diseases, to detect peripheral blood involvement, and to monitor responses to therapy.
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital and the Harvard Skin Disease Research Center, Boston, MA 02115, USA. rclark1@partners.org
authors.forename: Rachael A
authors.initials: RA
authors.lastname: Clark
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Shackelton
authors.forename: Rei
authors.initials: R
authors.lastname: Watanabe
authors.forename: Adam
authors.initials: A
authors.lastname: Calarese
authors.forename: Kei-ichi
authors.initials: K
authors.lastname: Yamanaka
authors.forename: James J
authors.initials: JJ
authors.lastname: Campbell
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Teague
authors.forename: Helen P
authors.initials: HP
authors.lastname: Kuo
authors.forename: DirkJan
authors.initials: D
authors.lastname: Hijnen
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Kupper
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D002469:Cell Separation; D029968:Escherichia coli Proteins; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D019674:Genes, T-Cell Receptor beta; D006801:Humans; D008213:Lymphocyte Activation; D016410:Lymphoma, T-Cell, Cutaneous / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D009182:Mycosis Fungoides / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009367:Neoplasm Staging; D012878:Skin Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors
chemical_list: D029968:Escherichia coli Proteins; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C512271:PhnF protein, E coli; D014157:Transcription Factors