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ANP32B suppresses B-cell acute lymphoblastic leukemia development through activation of PU.1 in mice

ABSTRACT: The acidic leucine-rich nuclear phosphoprotein 32B (ANP32B) is critical for maintenance of normal and leukemia stem cells. However, no data exist on ANP32B requirement in B-cell acute lymphoblastic leukemia (B-ALL) progression. Here, we observe that ANP32B is lowly expressed in B-ALL patients, which correlates with poor prognosis. Furthermore, we utilize N-myc or BCR-ABLp190-induced B-ALL mouse model to investigate the role of ANP32B in B-ALL development. Intriguingly, conditional deletion of Anp32b in hematopoietic cells significantly promotes leukemogenesis in B-ALL. Mechanistically, ANP32B interacts with PU.1 and enhances the transcriptional activity of PU.1 in B-ALL cells. Overexpression of PU.1 dramatically suppresses B-ALL progression, and highly expressed PU.1 significantly reverses the accelerated leukemogenesis in Anp32b-deficient mice. Collectively, our findings firstly identify ANP32B as a suppressor gene and provide novel insight into B-ALL pathogenesis.

ORGANISM(S): Mus musculus

PROVIDER: GSE214199 | GEO | 2025/09/24

REPOSITORIES: GEO

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