[The value of T-cell receptor gene rearrangement in the auxiliary diagnosis of T-cell large granular lymphocytic leukemia].

To explore the characteristics and auxiliary diagnostic value of T-cell receptor (TCR) gene rearrangement in T-cell abnormal clonal diseases, including T-cell large granular lymphocytic leukemia (T-LGLL) . Altogether, 103 newly diagnosed patients with T-LGLL, 18 with aplastic anemia (AA), 3 with pure red cell aplasia, 111 with systemic lupus erythematosus (SLE), and 30 healthy controls admitted at Jiangsu Province Hospital from September 2011 to November 2023 were enrolled. TCR gene rearrangement was detected by polymerase chain reaction and capillary electrophoresis, and TCRβ chain variable region (TCRVβ) subfamily and TCRβ chain constant region 1 (TRBC1) were detected by flow cytometry. The auxiliary diagnostic value of these three detection methods for T-LGLL was compared. Meanwhile, Sanger sequencing was used to detect STAT3 gene mutations in T-LGLL patients, and the mutation characteristics and clinical features of these patients were analyzed. In T-LGLL patients, 57 were men and 46 were women, and the patients' median age was 61 (28-81) years. Altogether, 97.1% (100/103) of the patients were positive for TCR gene rearrangement, and TCRβ gene rearrangement showed the highest incidence (95.1%, 98/103). TCRβ gene rearrangements were further classified into TCRβ (V-J) (42.9%, 42/98), TCRβ (D-J) (15.3%, 15/98), and copositive for two TCRβ gene rearrangements (41.8%, 41/98). This was followed by TCRγ (47.6%, 49/103) and TCRδ (4.9%, 5/103) gene rearrangements. The detection rates of TCRVβ and TRBC1 were 89.5% (51/57) and 73.5% (25/34), respectively. The detection rate of TRBC1 was significantly lower than that of TCR gene rearrangement (=0.004). The detection rates of TCR gene rearrangement in the AA, SLE, and healthy control groups were 19.0%, 6.3%, and 3.3%, respectively. Compared with healthy controls and SLE patients, the T-LGLL patients had significantly lower HGB, RBC, and ANC but significantly higher absolute lymphocyte count (ALC) (all <0.01). Compared with the AA group, the white blood cell count, ALC, and platelet counts of the T-LGLL patients were significantly higher (all <0.001). Compared with the AA, SLE, and healthy control groups, the T-LGLL patients were older and had a significantly higher detection rate of TCR gene rearrangement (all <0.05). Within the T-LGLL cohort, patients with positive TCRβ (D-J) gene rearrangement had significantly lower incidence of autoimmune diseases (3.6% 19.1%, =0.011) and HGB of ≥100 g/L (33.9% 63.8%, =0.002), but a significantly higher incidence of B symptoms (64.3% 38.3%, =0.009), than those patients without this rearrangement. Meanwhile, patients with positive TCRγ gene rearrangement had significantly higher incidence of STAT3 gene mutations (58.3% 30.2%, =0.012). The median follow-up time and overall survival (OS) rate of T-LGLL patients were 43 (3-178) months and 95.1% (98/103), respectively. No significant difference in the OS was observed among the patients with different types of TCR gene clonal rearrangements (all >0.05) . The detection rate of TCR gene rearrangement for T-cell clones is higher than that of TCRVβ and TRBC1. Patients with positive TCRβ (D-J) gene rearrangement have a higher incidence of B symptoms, lower incidence of autoimmune diseases, and lower HGB levels. Patients with positive TCRγ gene rearrangement are more likely to develop STAT3 gene mutation. These characteristics may be helpful in the differential diagnosis of T-LGLL.