# Molecular Markers Distinguishing Early‐Stage Mycosis Fungoides From Atopic Dermatitis Skin Lesions

## TL;DR

This study identifies molecular markers that can distinguish early-stage mycosis fungoides from atopic dermatitis skin lesions using single-cell RNA sequencing.

## Contribution

The study reveals novel transcriptomic features of early-stage mycosis fungoides compared to atopic dermatitis.

## Key findings

- Keratinocytes in mycosis fungoides show increased interferon response and proliferation genes.
- Fibroblasts in mycosis fungoides exhibit tumor-associated gene programs.
- Malignant T-cells in mycosis fungoides express exhaustion-associated markers.

## Abstract

Mycosis fungoides (MF) is the most common type of primary cutaneous T‐cell lymphoma, a disease characterized by malignant T cells that home to the skin. In early stages, clinical presentation is often indistinguishable from benign chronic inflammatory skin diseases such as atopic dermatitis (AD), posing a challenge for proper diagnosis and treatment. Previous studies have established that MF is characterized by the expansion of a single T‐cell clone, whereas benign skin conditions are polyclonal in nature. In this study, we aimed to use single‐cell RNA sequencing data to detect distinct transcriptomic features of early‐stage MF in comparison to AD skin. In early‐stage MF, we observed gene expression differences in cells of both the stroma and the immune system, with keratinocytes exhibiting increased interferon response and proliferation (STAT1, ICAM1, HLA‐DRA, GJB2), while fibroblasts displayed tumour‐associated programs (CXCL2, TNFAIP6, CEBPD). Myeloid cells exhibited expression of immunomodulatory genes (RUNX3, DDIT4, IL4I1), and malignant T‐cells expressed exhaustion‐associated markers (CXCL13, SOCS3, F2R, ETV1), as opposed to AD and healthy control samples. Thus, our results provide a novel insight into the immune‐stroma crosstalk in the tissue microenvironment of early‐stage MF vs. AD skin lesions.