| First Author | Dardaei L | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 5 | Pages | e96711 |
| PubMed ID | 24809472 | Mgi Jnum | J:216083 |
| Mgi Id | MGI:5607681 | Doi | 10.1371/journal.pone.0096711 |
| Citation | Dardaei L, et al. (2014) The deficiency of tumor suppressor prep1 accelerates the onset of meis1- hoxa9 leukemogenesis. PLoS One 9(5):e96711 |
| abstractText | Prep1 and Meis1 ortholog TALE transcription factors have opposing roles in tumorigenesis: Meis1 serves as an oncogene, Prep1 as a tumor suppressor. We now report that, Meis1 overexpression in primary Prep1-deficient (Prep1i/i) embryonic hematopoietic cells increases self-renewal potential of cells in vitro but not in vivo, whereas leukemia is instead obtained when Meis1 is combined with another oncogene, HoxA9. Prep1i/i Meis1-HoxA9-generated leukemic cells are less differentiated and grow more aggressively after the second passage in the mouse. These data indicate that Prep1 represents a barrier to the transforming activity of Meis1 in vitro, but its absence is not sufficient to induce early leukemogenesis. On the other hand, the Prep1i/i background appears to favor the insurgence of mutations that cause a more aggressive Meis1-HoxA9-generated leukemia. Indeed, the Prep1i/i leukemic cells upregulate the Polycomb protein Bmi-1 and expectedly down-regulate the Ink4a/Arf locus products. Finally, an important feature contributed by the Prep1i/i background is the post-transcriptional increase in Meis1 protein level. |
