Distribution of STAT3 mutations throughout gene domains and patient cohort. (A) STAT3 mutations (blue dots represent mutations in T-LGL; green dots, in CLPD-NKs) found in the SH2 domain, necessary for receptor association and tyrosine phosphodimer formation. The major domains of STAT3 are shown: coiled-coil domain, DNA-binding domain, SH2 domain, and transactivation domain. Lower panel: Corresponding representative Sanger sequence for each mutation found. (B) Percentage of patients with STAT3 mutations. Lesions were observed in 15 of 50 CLPD-NKs and 33 of 120 T-LGL patients when using Sanger and AS-PCR (7 cases not detected by Sanger). (C) Histograms showing the percentage of cases corresponding to each mutation. D661Y and Y640F accounted for ∼ 80% of all mutations found.