| First Author | Yang S | Year | 2021 |
| Journal | Blood | Volume | 138 |
| Issue | 24 | Pages | 2485-2498 |
| PubMed ID | 34359074 | Mgi Jnum | J:344058 |
| Mgi Id | MGI:7260030 | Doi | 10.1182/blood.2020010400 |
| Citation | Yang S, et al. (2021) ANP32B-mediated repression of p53 contributes to maintenance of normal and CML stem cells. Blood 138(24):2485-2498 |
| abstractText | Proper regulation of p53 signaling is critical for the maintenance of hematopoietic stem cells (HSCs) and leukemic stem cells (LSCs). The hematopoietic cell-specific mechanisms regulating p53 activity remain largely unknown. Here, we demonstrate that conditional deletion of acidic leucine-rich nuclear phosphoprotein 32B (ANP32B) in hematopoietic cells impairs repopulation capacity and postinjury regeneration of HSCs. Mechanistically, ANP32B forms a repressive complex with p53 and thus inhibits the transcriptional activity of p53 in hematopoietic cells, and p53 deletion rescues the functional defect in Anp32b-deficient HSCs. Of great interest, ANP32B is highly expressed in leukemic cells from patients with chronic myelogenous leukemia (CML). Anp32b deletion enhances p53 transcriptional activity to impair LSC function in a murine CML model and exhibits synergistic therapeutic effects with tyrosine kinase inhibitors in inhibiting CML propagation. In summary, our findings provide a novel strategy to enhance p53 activity in LSCs by inhibiting ANP32B and identify ANP32B as a potential therapeutic target in treating CML. |
