SBNO2 is an essential direct transcriptional target of mutated STAT3. (A) GSEA analysis of differentially expressed genes between HPC7 cells expressing STAT3 or STAT3^Y640F (blue) or primary CD8⁺ cells from patients with T-LGLL expressing either WT (n = 5) or mutated STAT3 (expressing: Y640F, n = 4; D661Y, n = 3; D661H, n = 1; D661V, n = 1; D661V+Y640F, n = 1) (red). (B) Heat map of commonly regulated genes (FDR < 0.05) between STAT3^Y640F-expressing mouse HPC7 cell lines and samples from patients with T-LGLL. Genes that are stronger bound by STAT3^Y640F are annotated in red on the right. (C) Overlap of genes that are overexpressed in murine and human STAT3-mutation–driven cells (i), are stronger bound by STAT3^Y640F (top) (ii), and represent selective dependencies in STAT3^Y640F-driven HPC7 cells (bottom) (iii). (D) Normalized expression of Sbno2 in HPC7 cells expressing either STAT3, STAT3^Y640F, or empty vector (mean ± SD, n = 3). (E) Normalized expression of SBNO2 in healthy CD8⁺ T cells (n = 5) or T-LGLL cells expressing either WT (n = 5) or mutant (n = 10) STAT3 (mean ± SD). Levels of significance were calculated using unpaired t-tests in panels D-E. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001. FDR, false discovery rate. GSEA Gene set enrichment analyses.