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Updated: May 6, 2026
Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells
Published on: February 21, 2018
BCL6B suppresses acute myeloid leukemia progression by transcriptionally repressing GGT5 and modulating MAPK
Yuqing Pan1,2,3, Kun Wu1,2,3, Xiaobo Ma1,2,3
1Department of Clinical Laboratory, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China.
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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