The leukemic oncoprotein NPM1-RARA inhibits TP53 activity

Abstract

The variant acute promyelocytic leukemia (APL) translocation t(5;17)(q35;q21) fuses the N-terminus of nucleophosmin (NPM1) to the retinoic acid receptor alpha (RARA). We found that ectopic NPM1-RARA expression decreased TP53 protein levels in target cells. NPM1-RARA impaired TP53-dependent transcription. Cells expressing NPM1-RARA were more resistant to apoptotic stimuli. This work identifies the TP53 tumor suppressor as a novel target through which NPM1-RARA impacts leukemogenesis, and confirms the importance of impairment of TP53 in establishment of the APL phenotype.

Keywords:

• Acute promyelocytic leukemia
• apoptosis
• NPM1-RARA
• nucleophosmin
• TP53

Acknowledgments

The authors wish to acknowledge Dr Richard Steinman for sharing reagents and helpful discussions. The work was supported by NIH R01CA67346 and P30CA047904.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article at http://dx.doi.org/10.3109/10428194.2015.1124992.