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Published on: January 7, 2019
Acute Promyelocytic Leukemia: A Paradigm for Oncoprotein-Targeted Cure
Hugues de Thé1, Pier Paolo Pandolfi2, Zhu Chen3
1Collège de France, PSL Research University, Chaire d'Oncologie Cellulaire et Moléculaire, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, INSERM UMR 944, CNRS UMR 7212, Hôpital St. Louis, Paris, France.
Abstract:
Recent clinical trials have demonstrated that the immense majority of acute promyelocytic leukemia (APL) patients can be definitively cured by the combination of two targeted therapies: retinoic acid (RA) and arsenic. Mouse models have provided unexpected insights into the mechanisms involved. Restoration of PML nuclear bodies upon RA- and/or arsenic-initiated PML/RARA degradation is essential, while RA-triggered transcriptional activation is dispensable for APL eradication. Mutations of the arsenic-binding site of PML/RARA, but also PML, have been detected in therapy-resistant patients, demonstrating the key role of PML in APL cure. PML nuclear bodies are druggable and could be harnessed in other conditions.
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