Early markers and drivers of cutaneous T-cell lymphoma in atopic dermatitis patients via transcriptomic/genomic profiling

Summary: Abstract Body: Cutaneous T-cell lymphoma (CTCL) is a rare form of non-Hodgkin's lymphoma predominantly affecting the skin. Atopic dermatitis (AD) and CTCL share clinicopathologic features, complicating early CTCL detection. A history of AD is further linked to higher CTCL prevalence and worse outcomes. This study identified early diagnostic markers and drivers of CTCL in patients with a history of AD using spatial transcriptomic and genomic profiling. Skin biopsies were collected from three male patients with AD diagnosed >2 years prior to CTCL (ages 64.3±0.9 yrs; stages IB-IVA; AD-to-CTCL time: 6±3 yrs; all used biologics for AD). For each patient, one biopsy diagnostic of AD and another of CTCL were analyzed using Xenium In Situ. We identified seven differentially expressed genes only in AD biopsies, 102 shared by AD/CTCL biopsies, and 21 genes unique to CTCL biopsies (p < 0.05, |Log2FC| > 1.5). AD biopsies exhibited Th2 skewing/chronic inflammation, while CTCL biopsies demonstrated immune evasion and T-cell survival/proliferation. Notably, both the AD and CTCL biopsies expressed CTCL-associated genes typically absent in AD that may represent early markers of CTCL—GIMAP7 (supports T-cell survival through PI3K/AKT signaling), RHOV (facilitates immune cell infiltration by modulating cell adhesion), MAL2 (contributes to immune evasion by downregulating MHC-I), and NOTCH3 (promotes angiogenesis/tumor cell migration). Additionally, two genes with increased expression in CTCL biopsies and not AD biopsies may represent oncogenic drivers of CTCL progression—CCL22 (drives recruitment of immune-suppressive cells) and PTPRCAP (enhances TCR signaling to promote T-cell survival and proliferation). These findings elucidate the molecular differences between AD and CTCL and identify potential biomarkers to improve CTCL detection and treatment in AD patients. Currently, we are integrating spatial data through pathway enrichment analysis and ligand-receptor interaction mapping within tissue niches to further clarify disease mechanisms. Jeffrey Weiner¹, Sara Khoshniyati¹, Namya Nanda¹, Jongbin Park¹, Martin Alphonse¹, Sima Rozati¹ 1. Dermatology, Johns Hopkins University, Baltimore, MD, United States. Translational Studies: Preclinical