Comprehensive transcriptional and clonotypic analysis of peripheral blood constituents in Sézary syndrome.

Although central to the diagnosis of cutaneous T cell lymphoma (CTCL) is the malignant clonal proliferation of skin-tropic T cells the diagnosis represents a spectrum of diseases and clinical courses. Most patients have an indolent disease course with cycling of therapies, while others, especially in advanced stages of disease, have aggressive progression and poor median survival. Adding to the difficulty of treatment, Sézary syndrome (SS), a leukemic variant of CTCL, lacks highly characteristic phenotypic and genetic markers that would aid in not only the diagnosis of the malignancy, but also response to therapies. 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. Overall design: CD45+ immune cells were isolated from peripheral blood of patients with Sezary Syndrome. Single-cell suspensions were processed with the Chromium Single Cell 5-prime Library & Gel Bead Kit and the 10x Genomics TCR Immunprofiling kit.