Examining Transcriptomic Differences Underlying Mycosis Fungoides in Skin of Color and White Patients

Abstract

Abstract Mycosis Fungoides (MF), the most common type of cutaneous T-cell lymphoma, typically presents with an erythematous or dyspigmented rash that can progress to tumors and ulcerations on the skin. MF is more common in skin of color (SOC) patients, where it presents earlier and at a higher T-stage. This has led to poorer prognosis in SOC patients, with the poorest prognosis in African Americans. The pathogenesis regarding this racial disparity remains poorly understood. We compared MF skin samples from SOC and White patients to determine differentially expressed genes and elucidate transcriptomic differences. An immune panel of 343 genes were hybridized to 8 MF SOC and 8 MF White skin samples. The resulting gene signatures were analyzed to determine significant differentially expressed genes. Analysis revealed that SOC has significant downregulation of critical immune response genes involved in the recruitment of immune cells to sites of inflammation, including CCR1, CCR2, and CCR3. Genes involved in ‘chemokine signaling,’ ‘differentiation and maintenance of myeloid cells,’ and ‘cell migration and adhesion,’ were downregulated in SOC MF biopsies as compared to White skin MF biopsies. Furthermore, SOC MF biopsies have a greater abundance of mast cells, whereas White skin MF biopsies have a greater abundance of neutrophils. These transcriptomic differences suggest that MF may have a unique pathogenesis in SOC that involves significant downregulation of the host’s immune response. This potentially provides insight into the presentation of MF at a more advanced stage and aggressive course in SOC as compared to White skin. This insight may facilitate the development of immunotherapies targeted to SOC to address this racial disparity. SD - recipient of the Dermatology Foundation DRSA; JMR - recipient of the Skin of Color Society Reseach Grant; ASB - recipient of the American Skin Association Milstein Research Scholar Award for Melanoma/Non-Melanoma Skin Cancer