Novel Mutation in T-Cell Large Granular Lymphocytic Leukemia

T-cell large granular lymphocytic (LGL) leukemia is a rare clonal expansion of cytotoxic T-lymphocytes (CTLs) that is clinically associated with cytopenias (especially chronic neutropenia) and rheumatoid arthritis. To identify gene mutations pathogenically associated with T-cell LGL leukemia, investigators used whole-exome and RNA sequencing of CTLs and normal control cells from a patient with the disorder to identify acquired mutations in the CTL clone.

A point mutation was identified in exon 21 of the STAT3 gene, which encodes a transcription factor (signal transducer and activator of transcription 3 gene) leading to a D661V substitution and constitutive activation of STAT3 signaling. Exon 21 mutations also were present in the tumor cells …