| First Author | Sun Y | Year | 2018 |
| Journal | Cancer Cell | Volume | 34 |
| Issue | 4 | Pages | 643-658.e5 |
| PubMed ID | 30270123 | Mgi Jnum | J:283553 |
| Mgi Id | MGI:6202274 | Doi | 10.1016/j.ccell.2018.08.018 |
| Citation | Sun Y, et al. (2018) HOXA9 Reprograms the Enhancer Landscape to Promote Leukemogenesis. Cancer Cell 34(4):643-658.e5 |
| abstractText | Aberrant expression of HOXA9 is a prominent feature of acute leukemia driven by diverse oncogenes. Here we show that HOXA9 overexpression in myeloid and B progenitor cells leads to significant enhancer reorganizations with prominent emergence of leukemia-specific de novo enhancers. Alterations in the enhancer landscape lead to activation of an ectopic embryonic gene program. We show that HOXA9 functions as a pioneer factor at de novo enhancers and recruits CEBPalpha and the MLL3/MLL4 complex. Genetic deletion of MLL3/MLL4 blocks histone H3K4 methylation at de novo enhancers and inhibits HOXA9/MEIS1-mediated leukemogenesis in vivo. These results suggest that therapeutic targeting of HOXA9-dependent enhancer reorganization can be an effective therapeutic strategy in acute leukemia with HOXA9 overexpression. |
