The clinical significance of STAT3 mutation, LDH and β2-MG in T-cell large granular lymphocytic Leukemia

T-cell large granular lymphocytic leukemia (T-LGLL) is a rare lymphoproliferative disorder of cytotoxic T cells (CTLs) and often associated with autoimmune disorders. The signal transducer and activator of transcription 3 (STAT3) is an oncogene, and its activation plays a key role in cell signaling transduction pathways in many types of cancer. The aim of the current study was to analyze the characteristics of T-LGLL.

We did this by determining the mutation status of STAT3 in 28 patients presenting with T-LGLL and evaluating STAT3 status in association with serum level of lacticdehydrogenase (LDH) and β2-microglobulin (β2-MG). Flow cytometric analysis for immunophenotype and TCR variable β-chain (Vβ) was performed in the patients.

FC-Vβ analysis was performed in 26 patients, and 22 (84.6%) patients had a restricted Vβ reactivity pattern, with predominance of a single Vβ mAb reactivity. There was no significant difference between serum LDH levels, gender, age or symptoms at diagnosis (P=0.062), lymphocytosis, anemia (P=0.057), thrombocytopenia, splenomegaly, LGL count or STAT3 mutation status. However, high β2-MG levels (P=0.005), neutropenia (P=0.018) and pure red blood cell aplasia (PRCA) (P=0.001) all displayed a significant association with STAT3 mutations. In univariate analysis, treatment-free survival (TFS) was affected by STAT3 mutation status (P=0.008) and β2-MG (P=0.006). In multivariate analysis, only anemia (P<0.001) was found to be an independent risk factor of shorter TFS.

We found an incidence of STAT3 mutations of 21.4% in patients presenting with T-LGLL and two mutations, E616V and V671F, had not been previously reported. Our results further demonstrate the remarkable correlation of STAT3 mutation with anemia, neutropenia and β2-MG. β2-MG and LDH is commonly used laboratory indicators, and detecting of them is helpful in estimating clinical characteristics and guiding treatment. We conclude from our data that FC-Vβ analysis is a fast and relatively economical alternative approach that can be used as a powerful tool in screening patients with suspected T-LGLL. Our study not only confirmed some of the previously reported observations, but it also provided new information on clinical associations, laboratory findings, prognostic factors, therapy and outcome in these patients.

No relevant conflicts of interest to declare.