STAT3 mutations specific to hematopoietic and lymphoid tissue were downloaded from COSMIC and cBio portal (STAT3 accession # NM_139276) and shown as lollipop plots. Domains are N-terminal, coiled-coil, DNA binding, linker, Src homology 2 (SH2), and transactivation (TA) (A-D). STAT3 mutation frequency is listed for (A) LGL leukemia (B) ATL, MDS, and NK/T lymphoma, and (C) all other hematological malignancies. Green, black, red, and pink circles indicate missense, truncation, in-frame, or other mutations, respectively. (D) STAT3 (alpha isoform) and STAT5B Homo sapiens amino acid sequences were retrieved from the NCBI Protein Database (accession # NP_644805 for STAT3, NP_036580 for STAT5B). The sequences were aligned using Clustal Omega, The C-terminal sequence including the SH2 and TA domains are shown. Asterisks indicate a fully-conserved amino acid at a position, while colons and periods indicate conserved and semi-conserved substitutions, respectively. STAT3 and STAT5B somatic mutations are annotated in red and blue, respectively. In two cases (Y640F and N647I) the STAT3 mutation creates the innate STAT5B amino acid.