Epigenetic alteration in HTLV-1–infected cells within asymptomatic carriers. (A) Box plot showing EZH2 expression in subpopulations from HTLV-1–infected individuals. P, D, and N represent subpopulations from indolent ATL (n = 3) and asymptomatic HTLV-1 carriers (n = 2). P indicates CD7⁺/CADM1⁻ cells; D indicates CD7⁺/CADM1⁺ cells; N indicates CD7⁻/CADM1⁺ cells. Acu-N indicates CD7⁻/CADM1⁺ cells from acute-type ATL. (B) Box plot showing relative expression levels of the H3K27me3-dependent silenced 856 genes (defined in supplemental Figure 4) in the subpopulations from HTLV-1–infected individuals and acute-type ATL (*P < 1E−4). (C) Venn diagram showing the relationship between disease progression and H3K27me3 gain. The 3 subgroups were classified according to the disease stages (stage I indicates P to D progression; stage II indicates D to N progression; stage III indicates indolent N to acute-type N progression). Each gene set was defined as (1) H3K27me3 gain (LogFC > 1) in acute-type ATL compared with normal CD4⁺ T cells and (2) decreased expression (FC < −1.5, P < .05) at the stages. (D) Microscopy data showing representative H3K27me3 level in CD4⁺/CADM1⁺ and CD4⁺/CADM1⁻ subpopulations within asymptomatic carriers (n = 3). The scale bars indicate 20 μm. (E) Graph showing the results of μChIP assay with anti-H3K27me3 antibody and control IgG in CD4⁺/CADM1⁺ and CD4⁺/CADM1⁻ subpopulations derived from asymptomatic carriers (n = 3, mean ± SD). Promoter region of the H3K27me3-regulated genes were tested. (F) Graph showing the population size of CD4⁺/CADM1⁺ cells in the presence or absence of 5 μM GSK126 treatment of 9 days (n = 14; *P < .05).