Recurrent alterations of TNFAIP3 (A20) in T-cell large granular lymphocytic leukemia

The pathogenesis of T-cell large granular lymphocytic leukemia (T-LGL) is poorly understood, as STAT3 mutations are the only known frequent genetic lesions. Here, we identified non-synonymous alterations in the TNFAIP3 tumor suppressor gene in 3 of 39 T-LGL. In two cases these were somatic mutations, in one case the somatic origin was likely. A further case harbored a SNP that is a known risk allele for autoimmune diseases and B cell lymphomas. Thus, TNFAIP3 mutations represent recurrent genetic lesions in T-LGL that affect about 8% of cases, likely contributing to deregulated NF-κB activity in this leukemia. What's New? T-cell large granular lymphocytic leukemia (T-LGL) is often associated with mutations in the STAT3 gene, but associations with other genetic mutations remain unknown. Here the authors identified non-synonymous mutations in the gene encoding TNF-alpha-induced protein 3 (TNFAIP3), a negative regulator of NF-kappa B signaling, in three patients with T-LGL. The study underscores the important role of NF-kappa B activity in this otherwise poorly understood lymphoid malignancy.