Mutations Y640F and D661Y and their relationship with large granular lymphocytic leukemia in NK and T-cells

Large granular lymphocytic leukemia (LGL) is a lymphoproliferative disorder that includes both T-LGL and NK-LGL. The aim of this study was to identify Y640F or D661Y mutations in T-LGL and NK-LGL. and their association with clinical features. Tetra-primer amplification refractory mutation system (ARMS) PCR was used to identify Y640F and D661Y mutations in the STAT3 gene. These mutations promote the survival of cytotoxic lymphocytes that exhibit clinical features associated with the mutated state. The characters lymphocytosis, treatment, and pure red cell aplasia (PRCA) were significant in T-LGL comparison with NK-LGL ( P ≤ 0.01 and P ≤ 0.05). While no statistically significant difference was observed in the incidence rates of neutropenia and anemia. The WBC (×10 9 /L) median was documented in T-LGL 7.3 and in NK-LGL 9.6 ( P ≤ 0.05). Anemia, PRCA, and rhematoid arthritis were significantly different in STAT3 mutation compared with no mutation ( P ≤ 0.01), while neutropenia, Thrombocytopenia, autoimmune hemolytic anemia, natural killer, and T-cell were not significantly different. The LGL count median (×10 9 ⁄ L) in STAT3 mutation was 2.30 ± 0.08 and in the non-mutant, it was 4.50 ± 0.19 ( P ≤ 0.01). There was no significant difference between Y640F and D661Y in both T-LGL and NK-LGL. The present study demonstrated that Y640F and D661Y were associated with an important role in the pathogenesis of NK-LGL and T-LGL and increased disease severity and abnormal clinical parameters.