%0 Journal Article
%T The spectrum of somatic mutations in large granular lymphocyte leukemia, rheumatoid arthritis, and Felty's syndrome.
%A Savola P
%A Bhattacharya D
%A Huuhtanen J
%J Semin Hematol
%V 59
%N 3
%D 07 2022
%M 36115688
%F 3.754
%R 10.1053/j.seminhematol.2022.07.004
%X T cell large granular lymphocyte leukemia (T-LGLL) is an interesting case at the intersection of autoimmunity and cancer. In T-LGLL, T cells with somatic pathogenic mutations (mainly in STAT3) are linked to rheumatoid arthritis (RA) and neutropenia. A rare subtype of RA, Felty's syndrome, exhibits overlapping clinical features and comparable frequencies of activating STAT3 mutations in T cells as T-LGLL, which hints at a potential T-LGLL-Felty's syndrome-RA axis. Somatic mutations could shed light on the unexplained pathologies of these disorders. However, the causality of somatic mutations-do somatic mutations in immune cells cause inflammation, or does prolonged inflammation predispose to mutagenesis-remains unanswered. This review will focus on the recent advances in understanding somatic mutations in T-LGLL and related autoimmune conditions as a master regulatory network that sustains lymphoproliferation and inflammation.