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  • Title: The spectrum of somatic mutations in large granular lymphocyte leukemia, rheumatoid arthritis, and Felty's syndrome.
    Author: Savola P, Bhattacharya D, Huuhtanen J.
    Journal: Semin Hematol; 2022 Jul; 59(3):123-130. PubMed ID: 36115688.
    Abstract:
    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.
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