Multimodal single cell analysis of molecular profiles of paired tissues of cutaneous T cell lymphoma. Multimodal single cell analysis of molecular profiles of paired tissues of cutaneous T cell lymphoma

Cutaneous T cell lymphoma (CTCL) is a heterogeneous group of mature T cell neoplasms characterized by the accumulation of clonal malignant CD4+ T cells in the skin. The most common variant of CTCL, Mycosis Fungoides, is confined to the skin in early stages but can be accompanied by extracutaneous dissemination of malignant T cells to the blood and lymph nodes in advanced stages of disease. Sézary Syndrome, a leukemic form of disease is characterized by significant blood involvement. Little is known about the transcriptional and genomic relationship between skin and blood residing malignant T cells in CTCL. In the present study we interrogate multiple modalities of information in single cells from matched skin and blood samples of patients with leukemic disease and healthy controls within a single workflow. By employing expanded CRISPR-compatible cellular indexing of transcriptomes and epitopes by sequencing (ECCITE-seq), we sought to compare the molecular profile of malignant clones residing in the skin and circulation of these patients across gene and protein expression modalities. We apply inferred CNV and phylogenetic analysis to examine sub-clonal heterogeneity to gain insights into the evolution and the relationship of malignant clones across tissues. Our data reveals clonal evolution at a transcriptional and genetic level within the malignant populations of individual patients. We highlight highly consistent transcriptional signatures delineating skin-derived and blood-derived malignant T cells. Analysis of these two populations suggests that environmental cues, along with genetic aberrations, contribute to transcriptional profiles of malignant T cells. Overall design: ECCITE-seq gene expression, antibody derived tag, and TCR clonotype profiles of matched skin and blood from 5 Sézary syndrome (SS) and leukemic Mycosis Fungoides (MF) patients and a healthy control. We also include ECCITE-seq profiles from 2 additional SS patients. >>>Submitter states that raw data will be made available at dbGaP due to patient privacy concerns<<<