T-bet suppresses proliferation of malignant B cells in chronic lymphocytic leukemia.

ABSTRACT:

Abstract

The T-box transcription factor T-bet is known as a master regulator of the T-cell response but its role in malignant B cells has not been sufficiently explored. Here, we conducted single-cell resolved multi-omics analyses of malignant B cells from patients with chronic lymphocytic leukemia (CLL) and studied a CLL mouse model with a genetic knockout of Tbx21. We found that T-bet acts as a tumor suppressor in malignant B cells by decreasing their proliferation rate. NF-κB activity, induced by inflammatory signals provided by the microenvironment, triggered T-bet expression, which affected promoter-proximal and distal chromatin coaccessibility and controlled a specific gene signature by mainly suppressing transcription. Gene set enrichment analysis identified a positive regul

SUBMITTER: Roessner PM 

PROVIDER: S-EPMC11307267 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature