261 Single-cell analyses reveal novel molecular signatures and pathogenesis in cutaneous T cell lymphoma

Sézary syndrome (SS), the leukemic variant of cutaneous T-cell lymphoma, is characterized by presence malignant cells (Sézary cells, SCs) in both blood and skin. Insights into molecular progression SS have revealed substantial inter- intra-tumoral heterogeneity. Identifying common gene expression signature from different compartments elucidating disease pathogenesis could facilitate diagnosis treatment as a whole. Here we performed comprehensive analysis integrating single-cell transcriptomic data peripheral mononuclear (BMCs) skin well chromatin accessibility PBMCs patients healthy controls (HCs). What's more, samples patients, MF PE HCs, multiple cell lines, were used to conduct validation experiments. Phenotypic plasticity between blood- skin-derived (SCs) was investigated series potential biomarker genes that facilitated diagnoses prognosis prediction MF/SS, including reported (TOX, DNM3, KLHL42) novel (PGM2L1 SESN3) genes, revealed. In addition, present study described mechanism tumor be promoted GATA3 regulation KLHL42, further clarifying CTCL providing therapeutic targets for CTCL.