| First Author | Korf K | Year | 2014 |
| Journal | Proc Natl Acad Sci U S A | Volume | 111 |
| Issue | 33 | Pages | 12133-8 |
| PubMed ID | 25092303 | Mgi Jnum | J:213929 |
| Mgi Id | MGI:5586911 | Doi | 10.1073/pnas.1412944111 |
| Citation | Korf K, et al. (2014) The PML domain of PML-RARalpha blocks senescence to promote leukemia. Proc Natl Acad Sci U S A 111(33):12133-8 |
| abstractText | In most acute promyelocytic leukemia (APL) cases, translocons produce a promyelocytic leukemia protein-retinoic acid receptor alpha (PML-RARalpha) fusion gene. Although expression of the human PML fusion in mice promotes leukemia, its efficiency is rather low. Unexpectedly, we find that simply replacing the human PML fusion with its mouse counterpart results in a murine PML-RARalpha (mPR) hybrid protein that is transformed into a significantly more leukemogenic oncoprotein. Using this more potent isoform, we show that mPR promotes immortalization by preventing cellular senescence, impeding up-regulation of both the p21 and p19(ARF) cell-cycle regulators. This induction coincides with a loss of the cancer-associated ATRX/Daxx-histone H3.3 predisposition complex and suggests inhibition of senescence as a targetable mechanism in APL therapy. |
