BCL6B suppresses acute myeloid leukemia progression by transcriptionally repressing GGT5 and modulating MAPK signaling

In this study, we investigated the role of B-cell lymphoma 6 member B (BCL6B) in AML progression. Integrated analyses of TCGA-LAML, GTEx, and GEO datasets revealed that BCL6B was significantly downregulated in AML and associated with adverse clinical features and shorter overall survival.

Functional assays demonstrated that BCL6B overexpression suppressed AML cell proliferation, induced apoptosis, and caused G0/G1 cell cycle arrest, whereas BCL6B knockdown exerted opposite effects. Mechanistically, transcriptome analysis and promoter-binding assays identified gamma-glutamyltransferase 5 (GGT5) as a direct transcriptional target of BCL6B. BCL6B bound to the GGT5 promoter and repressed its expression, thereby modulating MAPK signaling by inhibiting ERK phosphorylation and activating p38 and JNK pathways.