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

Abstract

ANP32B, a member of the acidic leucine-rich nuclear phosphoprotein 32 kDa (ANP32) family of proteins, is critical for normal development because its constitutive knockout mice are perinatal lethal. It is also shown that ANP32B acts as a tumor-promoting gene in some kinds of cancer such as breast cancer and chronic myelogenous leukemia. Herein, we observe that ANP32B is lowly expressed in B-cell acute lymphoblastic leukemia (B-ALL) patients, which correlates with poor prognosis. Furthermore, we utilized the 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 two B-ALL mouse models. Mechanistically, ANP32B interacts with purine rich box-1 (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 identify ANP32B as a suppressor gene and provide novel insight into B-ALL pathogenesis.