CTCL hallmark gene CD82 regulates proliferation and apoptosis via the JAK-STAT signaling pathway. (A) Genes CD82, CCR4, and KIR3DL2 displayed a similar monotonical expression pattern increasing from normal to intermediate to CTCL groups. (B) Mean fluorescence intensity (MFI) of CD82 protein expression in CD4⁺ CTCL cells compared with normal CD4⁺ T cells from CTCL patient–derived PBMCs (n = 9; 1-tailed t test). (C) Representative histograms comparing CD82 expression in purified CTCL cells that have undergone either CD82 knockout (CD82-KO, blue) or mock knockout (CD82-NC [negative control], red). (D) Bulk RNAseq was used to confirm CD82 expression in purified CTCL cells before and after CD82 knockout. (E) Comparison of the relative percentage of CTCL cell proliferation in CD82 knockout and mock knockout CTCLs (n = 4; 1-tailed paired t test). (F) Representative flow cytometric analysis of the proliferative capacity of CTCL cells (CD82-KO and CD82-NC) cultured for 2 days after anti-CD3+anti-CD28 stimulation for 2 days. (G) Comparison of the percentage of apoptotic cells present in CD82 knockout and mock knockout CTCLs in the proliferation experiment in panel E. (H) Comparison of the relative level of phosphorylation of JAK2, JAK3, STAT5, AKT1, and PI3K in activated and proliferated CTCL cells after CD82 knockout or mock knockout cells cultured for 2 days after anti-CD3+anti-CD28 stimulation for 2 days. (I) CTCL cells isolated from patient peripheral blood were incubated for 72 hours with a range of concentrations of various JAK inhibitors, from which the 50% inhibitory concentrations were calculated. Each dot represents a single patient’s response to a single drug.