KIR3DL2 promoter is hypomethylated in patients with acute-type ATL. (A) Differential methylation at the KIR3DL2 locus using the β-value method, measured in an Illumina 450K array-based methylome analysis in samples from patients with ATL (19 acute, 2 lymphoma, and 7 chronic/smoldering forms), 4 HTLV-1 carriers, and 4 healthy donors (isolated CD4⁺ TL). The KIR3DL2 promoter was significantly less methylated in acute-type ATL than in lymphoma- and chronic/smoldering-type ATLs or HTLV-1 ACs (unpaired t test). The proportion of tumor cells was greater than 85% in the acute-type ATL samples. Each dot represents an individual CpG per patient in the β-value analysis. The horizontal line represents the median, and the whiskers represent the range. (B) KIR3DL2 protein expression was induced on Hut 78 cells, but not on Jurkat cells, upon incubation with 5-aza (0, 1, 2, 4, 8, or 16 μM) for 3 days. The error bars correspond to the standard deviation. ****P < .0001; **P < .01 (2-way analysis of variance followed by Šidák’s post hoc test). MFI, mean fluorescence intensity. (C) 5-Aza led to hypomethylation of KIR3DL2 promoter, assessed by MS-MLPA, in Hut 78 cells treated with 5-aza from 1 μM. Experiment performed in triplicate. **P < .01 (unpaired t-test).