Impact of CpG island DNA methylation on ICOS expression. (A) Schematic diagram of the ICOS gene structure depicting the position of CpG island within intron 1 of the gene. (B) Patterns of CpG island methylation in various TCL-derived cell lines. (Top panel) ALK⁺ TCL-derived cell lines. (Bottom panel) Cell lines from cutaneous CD30⁺ lymphoproliferative disorder (2A and 2B) and CTCL (Sez-4, SeAx, MyLa2059, and MyLa3675). (C) Changes in ICOS gene CpG island methylation induced in SUDHL-1 cells by treatment with ADC for 0, 48, and 88 hours. (D) Increase in ICOS mRNA expression in ALK⁺ TCL cell lines treated with ADC for 96 hours detected by quantitative RT-PCR. (E) Flow cytometry–detected increase in ICOS protein expression in the depicted ALK⁺ TCL cell lines treated with ADC for 96 hours.