| First Author | Nishimoto N | Year | 2011 |
| Journal | Blood | Volume | 118 |
| Issue | 9 | Pages | 2541-50 |
| PubMed ID | 21757616 | Mgi Jnum | J:177091 |
| Mgi Id | MGI:5293593 | Doi | 10.1182/blood-2010-10-315440 |
| Citation | Nishimoto N, et al. (2011) Loss of AML1/Runx1 accelerates the development of MLL-ENL leukemia through down-regulation of p19ARF. Blood 118(9):2541-50 |
| abstractText | Dysfunction of AML1/Runx1, a transcription factor, plays a crucial role in the development of many types of leukemia. Additional events are often required for AML1 dysfunction to induce full-blown leukemia; however, a mechanistic basis of their cooperation is still elusive. Here, we investigated the effect of AML1 deficiency on the development of MLL-ENL leukemia in mice. Aml1 excised bone marrow cells lead to MLL-ENL leukemia with shorter duration than Aml1 intact cells in vivo. Although the number of MLL-ENL leukemia-initiating cells is not affected by loss of AML1, the proliferation of leukemic cells is enhanced in Aml1-excised MLL-ENL leukemic mice. We found that the enhanced proliferation is the result of repression of p19(ARF) that is directly regulated by AML1 in MLL-ENL leukemic cells. We also found that down-regulation of p19(ARF) induces the accelerated onset of MLL-ENL leukemia, suggesting that p19(ARF) is a major target of AML1 in MLL-ENL leukemia. These results provide a new insight into a role for AML1 in the progression of leukemia. |
