T-Bet Suppresses Proliferation of Malignant B Cells in CLL

New research has discovered a novel tumor suppressive role of the T-box transcription factor, T-bet, in malignant B cells. Specifically, T-bet acts as a tumor suppressor by enhancing interferon signaling and inhibiting proliferation of malignant B cells.

“Our study provides evidence for a so far unexplored role of T-bet in [chronic lymphocytic leukemia (CLL)] and provides insights into its transcriptional regulation and activity, as well as its prognostic role,” study researchers wrote in Blood.

The researchers conducted single-cell resolved multi-omics analyses of malignant B cells from patients with CLL and compared them with healthy, age-matched control samples. They also studied a CLL mouse model with genetic knockout of TBX21.

In the cells of patients with CLL, the investigators found higher TBX21 expression and T-bet protein levels than in the control group. Further analysis determined that inflammatory signals in the lymphoid tissue microenvironment spur NF-κB activity, which leads to T-bet expression in CLL cells. T-bet then represses the cell cycle of malignant B cells, decreasing their proliferation.

The researchers found that through this mechanism, T-bet expression in CLL cells was associated with longer overall survival in patients with CLL.

“Our study uncovered a novel tumor suppressive role of T-bet in malignant B cells via its regulation of inflammatory processes and cell cycling, which has implications for the stratification and therapy of patients with CLL,” the researchers wrote. “Linking T-bet activity to inflammation explains the good prognostic role of genetic alterations in the inflammatory signaling pathways in CLL.”

Reference

Roessner PM, Seufert I, Chapaprieta V, et al. T-bet suppresses proliferation of malignant B cells in chronic lymphocytic leukemia. Blood. 2024. doi:10.1182/blood.2023021990