| First Author | Mamo A | Year | 2006 |
| Journal | Blood | Volume | 108 |
| Issue | 2 | Pages | 622-9 |
| PubMed ID | 16469876 | Mgi Jnum | J:135648 |
| Mgi Id | MGI:3794227 | Doi | 10.1182/blood-2005-06-2244 |
| Citation | Mamo A, et al. (2006) Molecular dissection of Meis1 reveals 2 domains required for leukemia induction and a key role for Hoxa gene activation. Blood 108(2):622-9 |
| abstractText | The Hoxa9 and Meis1 genes represent important oncogenic collaborators activated in a significant proportion of human leukemias with genetic alterations in the MLL gene. In this study, we show that the transforming property of Meis1 is modulated by 3 conserved domains, namely the Pbx interaction motif (PIM), the homeodomain, and the C-terminal region recently described to possess transactivating properties. Meis1 and Pbx1 interaction domain-swapping mutants are dysfunctional separately, but restore the full oncogenic activity of Meis1 when cotransduced in primary cells engineered to overexpress Hoxa9, thus implying a modular nature for PIM in Meis1-accelerated transformation. Moreover, we show that the transactivating domain of VP16 can restore, and even enhance, the oncogenic potential of the Meis1 mutant lacking the C-terminal 49 amino acids. In contrast to Meis1, the fusion VP16-Meis1 is spontaneously oncogenic, and all leukemias harbor genetic activation of endogenous Hoxa9 and/or Hoxa7, suggesting that Hoxa gene activation represents a key event required for the oncogenic activity of VP16-Meis1. |
