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.

Super enhancer related gene ANP32B promotes the proliferation of acute myeloid leukemia by enhancing MYC through histone acetylation

“…1 D). Notably, previous studies have reported on the role of ANP32B in CML [ 16 ] and ALL [ 17 ], suggesting its general significance in leukemia. We focused on the role of ANP32B in AML.…”

“…Furthermore, ANP32B has been identified as an inhibitor of p53 activity, playing a crucial role in the regulation of both normal and CML stem cell maintenance [ 16 ]. However, a recent investigation has revealed that ANP32B exerts a suppressive effect on B-ALL in mice by activating PU.1 [ 17 ]. The findings imply that ANP32B potentially plays a multifaceted role in leukemia.…”