Transcription factor TOX as a novel biomarker in T cell large granular lymphocytic leukemia (T-LGLL)
T cell large granular lymphocytic leukaemia (T-LGLL) is a rare disorder that can cause unexplained cytopenias. It accounts for approximately 2-3% of all mature lymphoid leukemias. Identifying T-LGLL in bone marrow biopsies is challenging due to overlap with reactive processes and the lack of a robust immunohistochemistry marker. Current markers, such as granzyme B, TIA-1, and CD8, are difficult to interpret or lack specificity. This study investigates whether immunohistochemistry for thymocyte selection-associated high-mobility group box (TOX), a transcription factor associated with chronic T cell stimulation, could be a reliable tool for identifying T-LGLL cells.
In this retrospective study, we examined the expression of TOX in CD8+ cells in bone marrow biopsies of T-LGLL patients (n = 38) and compared it to bone marrow from controls with reactive T cell lymphocytosis (n = 10). All biopsies were evaluated for TOX staining within the CD8-positive T cell population by immunohisochemistry.
The control group showed minimal TOX expression, whereas all T-LGLL cases were positive (median = 80%, range = 10-100% of CD8-positive cells), even when bone marrow involvement was subtle. This high sensitivity of TOX suggests its potential as a reliable diagnostic marker for T-LGLL.
TOX is a highly sensitive marker for the neoplastic cells of T-LGLL and is recommended for use in bone marrow biopsies, especially in the diagnostic work-up of patients with unexplained cytopenias.