AI Article Synopsis
- * The study highlights that PML is essential for the process where RA induces NPM-1c degradation, activates P53, and triggers cell death.
- * RA increases PML expression by inhibiting Pin1, leading to P53 activation, which enhances the effectiveness of chemotherapy or arsenic treatment in these patients.
Article Abstract
Retinoic acid (RA) was proposed to increase survival of chemotherapy- treated patients with nucleophosmin-1 (NPM-1c)-mutated acute myeloid leukemia. We reported that, ex vivo, RA triggers NPM-1c degradation, P53 activation and growth arrest. PML organizes domains that control senescence or proteolysis. Here, we demonstrate that PML is required to initiate RA-driven NPM-1c degradation, P53 activation and cell death. Mechanistically, RA enhances PML basal expression through inhibition of activated Pin1, prior to NPM-1c degradation. Such PML induction drives P53 activation, favoring blast response to chemotherapy or arsenic in vivo. This RA/PML/P53 cascade could mechanistically explain RA-facilitated chemotherapy response in patients with NPM-1c mutated acute myeloid leukemia.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8634200 | PMC |
| http://dx.doi.org/10.3324/haematol.2020.274878 | DOI Listing |
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