Functional annotation of genes differentially expressed between IDH2/TET2 double-mutant AITL and TET2 single-mutant AITL. (A) Selected top IPA canonical pathways differing between IDH2/TET2 double-mutant AITL and TET2 single-mutant AITL. (B) IPA upstream analysis to predicted activation state of annotated proteins. “Vegf” and “Interferon alpha” are groups of proteins instead of single molecules. Activation z-score >3 was considered significant. (C) Apoptosis pathway identified by GSEA analysis significantly altered in IDH2/TET2 double-mutant AITL compared with TET2 single-mutant AITL. The normalized enrichment score, P value, and false discovery rate value are indicated. (D) Correlations between (1) the differences in GEP between each individual AITL case and the median tumor value with (2) the changes in GEP induced in normal CD4⁺ T-cells by IL-12 (48 hours). (E) Comparison of the number of “T_FH-up genes” and “T_FH-down genes” (see text) in AITL. Data are shown as mean ± standard error of the mean (SEM). P value was calculated using the 2-tailed Student t test. *P < .05, **P < .01, ***P < .001, and ****P < .0001.