T-cell large granular lymphocyte leukaemia with pure red cell aplasia harbouring a somatic STAT3 P715L mutation

T-cell large granular lymphocyte leukaemia (T-LGLL) is a chronic lymphoproliferative disorder often associated with pure red cell aplasia (PRCA). We report a unique case of a woman in her 50s presenting with PRCA secondary to T-LGLL, in which targeted next-generation sequencing identified a somatic STAT3 P715L mutation. This variant, previously described only in germline mutation in STAT3 gain-of-function syndrome, has not been reported as a somatic mutation in T-LGLL. Immunohistochemical analysis revealed constitutive STAT3 (signal transducer and activator of transcription 3) activation in clonal CD8⁺ T cells, suggesting a pathogenic role for the P715L mutation. The patient responded to ciclosporin therapy with gradual haematological improvement and became transfusion-independent within 6 months. This case highlights the importance of molecular profiling in T-LGLL presentations and expands the known mutational spectrum of STAT3 It also raises the possibility that non-SH2 (Src homology 2) domain STAT3 mutations may contribute to disease pathogenesis and influence treatment response in T-LGLL.