Regional DNA hypermethylation reflects ATL disease development and progression. (A) Unsupervised hierarchical clustering analysis using DNA methylation profiles of 1207 hypermethylated DMPs common to all 7 indolent ATL cases. (B) Average β values of the 1207 probes in each cell subpopulation (P, CADM1−/CD7+ [blue]; D, CADM1+/CD7dim+ [yellow]; N, CADM1+/CD7− [red]) from individuals and HTLV-1–infected T-cell lines (black). Differences between each subpopulation were tested using the Tukey-Kramer method. **P < .005. (C) Serial changes in the proportions of each subpopulation (P, CADM1−/CD7+ [blue]; D, CADM1+/CD7dim+ [yellow]; N, CADM1+/CD7− [red]) in CADM1 vs CD7 plots, and percentages of abnormal lymphocytes (black) in 2 asymptomatic carriers (ACs). Cell sorting and DNA extraction were performed before and after ATL development, as indicated by the black arrows. (D) Average β value of 470 870 probes (global DNA methylation) and 1207 probes (extracted DMPs in panel A) in ACs before and after ATL onset.