What question did this study set out to answer?

This research aims to clarify the function and mechanisms of BCL6B in acute myeloid leukemia.

May 7, 2026Open Access

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

Key Points

This research aims to clarify the function and mechanisms of BCL6B in acute myeloid leukemia.
Public datasets were analyzed for BCL6B expression patterns and prognostic relevance in AML.
Gain- and loss-of-function experiments were performed in AML cell lines.
In vivo validation used zebrafish and nude mouse xenograft models.
BCL6B expression was reduced in AML compared to normal controls; its higher levels correlated with prolonged overall survival.
Decitabine treatment restored BCL6B expression, suggesting epigenetic regulation involvement.
BCL6B overexpression induced apoptosis and inhibited cell proliferation and progression; GGT5 was identified as its direct transcriptional target.

Abstract

BACKGROUND: BCL6B has been implicated as a tumor suppressor in several solid malignancies; however, its biological function and molecular mechanisms in acute myeloid leukemia (AML) remain insufficiently defined. METHODS: Public datasets were analyzed to evaluate the expression pattern, diagnostic performance, and prognostic relevance of BCL6B in AML. Epigenetic regulation was explored using decitabine treatment. Gain- and loss-of-function experiments were conducted in AML cell lines to determine the effects of BCL6B on apoptosis, cell cycle progression, and proliferation. Transcriptome sequencing, dual-luciferase reporter assays, and electrophoretic mobility shift assays (EMSA) were performed to identify and validate downstream targets. MAPK pathway alterations were examined by Western blotting. Zebrafish and nude mouse xenograft models were used for in vivo validation. RESULTS: BCL6B expression was significantly reduced in AML compared with normal controls and demonstrated diagnostic value across molecular subgroups. Higher BCL6B expression was associated with prolonged overall survival, indicating that BCL6B may serve as a prognostically relevant biomarker. Decitabine treatment restored BCL6B expression, suggesting that BCL6B expression may be regulated by epigenetic mechanisms. Functionally, BCL6B overexpression promoted apoptosis, induced G0/G1 cell cycle arrest, and suppressed proliferation in AML cells, whereas BCL6B knockdown exerted opposite effects. Mechanistically, GGT5 was identified as a direct transcriptional target of BCL6B. BCL6B repressed GGT5 promoter activity and counteracted GGT5-mediated pro-proliferative and anti-apoptotic phenotypes. Pathway analyses revealed that BCL6B modulated MAPK signaling in a GGT5-dependent manner, characterized by decreased ERK phosphorylation and enhanced p38/JNK activation. In vivo, BCL6B overexpression suppressed tumor growth, migration, angiogenesis, and prolonged survival. CONCLUSIONS: BCL6B functions as a tumor suppressor in AML by transcriptionally repressing GGT5 and modulating MAPK signaling. These findings provide mechanistic insight into BCL6B-mediated leukemogenesis and support its potential as a diagnostic biomarker and therapeutic target.

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