RRBS assessment of changes in DNA methylation in NK-LGL patient samples compared with normal NK cells. (A) RRBS was used to assess DNA methylation in the same highly pure leukemic samples used for WGS (TET2 mutant [Mut], n = 3; TET2 WT, n = 3) compared with 5 purified NK cell samples from normal donors (Normal). Principal component analysis used high-variance cytosine-phosphate-guanine sites at the 0.9 percentile of the interquartile range. Number of data points = 239 696. (B) Comparison of number of hypermethylated (Hyper) and hypomethylated (Hypo) differentially methylated regions of TET2 Mut and TET WT leukemic samples vs normal NK cells. (C) Distribution and quartiles of the amount of individual cytosine methylation within promoters of negative regulators of STAT3 in which 1 = 100% methylated. (D) Representative PTRD promoter methylation–specific polymerase chain reaction, with all gels provided in supplemental Figure 5. (E) PTPRD promoter methylation within mutation subgroups (Fisher’s exact test, TET2 WT vs TET2 Mut [all samples] not significant, P = .0772; WT vs TET2 Mut, P = .0474. Co-Mut, comutation; NA, not applicable; PC, principal component.