Human NK-cell leukemia driven by STAT3 mutations depends on SBNO2 expression. (A) Normalized SBNO2 expression from patients with NK-cell leukemia (left) and from patients with T-NHL (right) with either mutated STAT3 (NK, n = 19; T-NHL, n = 34) or WT STAT3 (NK, n = 50; T-NHL, n = 56) have been depicted. Competitive proliferation assays in human NK-cell leukemia cell lines harboring either mutated STAT3 (NKYS) (B) or WT STAT3 (KAI3) (C), transduced with short hairpin RNA (shRNA) expression vectors targeting either Renilla (negative control), MYC (positive control), STAT3, or SBNO2. Relative abundance of shRNA⁺ cells was normalized to day 4 after transduction (mean ± SD, n = 3). (D) Quantitative polymerase chain reaction (qPCR) expression analyses of STAT3 or SBNO2 in NKYS cells 5 days after transduction with shRNA vectors targeting STAT3 or SBNO2, respectively (mean ± SD, n ≥ 3). Levels of significance were calculated using unpaired t-test in panel A. ∗∗P < .01.