Differential SATB1 expression reveals heterogeneity of cutaneous T cell lymphoma.

Abstract SATB1 is an important T-cell specific chromatin organizer in cutaneous T cell lymphoma, while its expression and function in Mycosis fungoides (MF) remain ambiguous. Our study aimed to investigate the clinicopathological significance of SATB1 in a cohort of 170 MF patients. SATB1 expression was heterogeneous among MF patients in each clinical stage. High SATB1 expression was associated with epidermal hyperplasia, eosinophil infiltration, less large-cell transformation, and favorable prognosis in MF cases. SATB1 and CD30 co-expression distinguished cutaneous CD30+ lymphoproliferative disorders from MF large-cell transformation. SATB1 silencing in MF lines showed that SATB1 upregulated genes involved in eosinophil recruitment, including STAT3 and IL13, and downregulated genes in cell cycle progression, which may explain the inferior prognosis for low SATB1-expressing cases. Moreover, SATB1 was inversely correlated with PD1 expression, indicating an exhausted status of SATB1-negative malignant T cells. SATB1 was positively correlated with TLRs expression, suggesting innate immune activation in high SATB1-expressing MF cases. Therefore, variable SATB1 expression promotes heterogeneity in pathology and clinical outcome of patients with MF.