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

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. Overall design: RNA-seq data from GFP+ BM cells from recipients receiving N-myc-transduced Anp32b+/+ and Anp32b-/-B220+ BM cells.