| First Author | Stanley RF | Year | 2017 |
| Journal | J Exp Med | Volume | 214 |
| Issue | 3 | Pages | 753-771 |
| PubMed ID | 28232469 | Mgi Jnum | J:241522 |
| Mgi Id | MGI:5902884 | Doi | 10.1084/jem.20162089 |
| Citation | Stanley RF, et al. (2017) A myeloid tumor suppressor role for NOL3. J Exp Med 214(3):753-771 |
| abstractText | Despite the identification of several oncogenic driver mutations leading to constitutive JAK-STAT activation, the cellular and molecular biology of myeloproliferative neoplasms (MPN) remains incompletely understood. Recent discoveries have identified underlying disease-modifying molecular aberrations contributing to disease initiation and progression. Here, we report that deletion of Nol3 (Nucleolar protein 3) in mice leads to an MPN resembling primary myelofibrosis (PMF). Nol3-/- MPN mice harbor an expanded Thy1+LSK stem cell population exhibiting increased cell cycling and a myelomonocytic differentiation bias. Molecularly, this phenotype is mediated by Nol3-/--induced JAK-STAT activation and downstream activation of cyclin-dependent kinase 6 (Cdk6) and MycNol3-/- MPN Thy1+LSK cells share significant molecular similarities with primary CD34+ cells from PMF patients. NOL3 levels are decreased in CD34+ cells from PMF patients, and the NOL3 locus is deleted in a subset of patients with myeloid malignancies. Our results reveal a novel genetic PMF-like mouse model and identify a tumor suppressor role for NOL3 in the pathogenesis of myeloid malignancies. |
