Single-cell analysis of Sézary syndrome reveals novel markers and shifting gene profiles associated with treatment.

Autor:	Borcherding N; Department of Pathology, University of Iowa, Iowa City, IA.; Department of Pathology and Immunology, Washington University, St. Louis, MO., Severson KJ; Department of Dermatology, Mayo Clinic, Scottsdale, AZ., Henderson N; Department of Dermatology, University of Iowa, Iowa City, IA., Ortolan LS; Department of Dermatology, University of Iowa, Iowa City, IA.; Seattle Children's Research Institute, Seattle, WA., Rosenthal AC; Department of Hematology Oncology, Mayo Clinic, Phoenix, AZ., Bellizzi AM; Department of Pathology, University of Iowa, Iowa City, IA., Liu V; Department of Pathology, University of Iowa, Iowa City, IA.; Department of Dermatology, University of Iowa, Iowa City, IA.; Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA., Link BK; Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA.; Department of Internal Medicine, University of Iowa, Iowa City, IA., Mangold AR; Department of Dermatology, Mayo Clinic, Scottsdale, AZ., Jabbari A; Department of Pathology, University of Iowa, Iowa City, IA.; Department of Dermatology, University of Iowa, Iowa City, IA.; Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA.; Iowa City Veterans Affairs Medical Center, Iowa City, IA.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2023 Feb 14; Vol. 7 (3), pp. 321-335.
DOI:	10.1182/bloodadvances.2021005991
Abstrakt:	Cutaneous T-cell lymphomas (CTCLs) are a spectrum of diseases with varied clinical courses caused by malignant clonal proliferation of skin-tropic T cells. Most patients have an indolent disease course managed with skin-directed therapies. In contrast, others, especially in advanced stages of disease or with specific forms, have aggressive progression and poor median survival. Sézary syndrome (SS), a leukemic variant of CTCL, lacks highly consistent phenotypic and genetic markers that may be leveraged to prevent the delay in diagnosis experienced by most patients with CTCL and could be useful for optimal treatment selection. Using single-cell mRNA and T-cell receptor sequencing of peripheral blood immune cells in SS, we extensively mapped the transcriptomic variations of nearly 50 000 T cells of both malignant and nonmalignant origins. We identified potential diverging SS cell populations, including quiescent and proliferative populations shared across multiple patients. In particular, the expression of AIRE was the most highly upregulated gene in our analysis, and AIRE protein expression could be observed over a variety of CTCLs. Furthermore, within a single patient, we were able to characterize differences in cell populations by comparing malignant T cells over the course of treatment with histone deacetylase inhibition and photopheresis. New cellular clusters after progression of the therapy notably exhibited increased expression of the transcriptional factor FOXP3, a master regulator of regulatory T-cell function, raising the potential implication of an evolving mechanism of immune evasion. (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Databáze:	MEDLINE
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