AI Article Synopsis
- * Research showed that RA and arsenic trioxide work together to degrade mutant NPM1 in AML cells, leading to cell differentiation and death.
- * Treatment with RA and arsenic was effective in reducing unhealthy bone marrow cells in three patients, suggesting potential benefits of this combination therapy for NPM1 mutant AML and highlighting the need for further clinical studies.
Article Abstract
Nucleophosmin-1 (NPM1) is the most frequently mutated gene in acute myeloid leukemia (AML). Addition of retinoic acid (RA) to chemotherapy was proposed to improve survival of some of these patients. Here, we found that RA or arsenic trioxide synergistically induce proteasomal degradation of mutant NPM1 in AML cell lines or primary samples, leading to differentiation and apoptosis. NPM1 mutation not only delocalizes NPM1 from the nucleolus, but it also disorganizes promyelocytic leukemia (PML) nuclear bodies. Combined RA/arsenic treatment significantly reduced bone marrow blasts in 3 patients and restored the subnuclear localization of both NPM1 and PML. These findings could explain the proposed benefit of adding RA to chemotherapy in NPM1 mutant AMLs, and warrant a broader clinical evaluation of regimen comprising a RA/arsenic combination.
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| http://dx.doi.org/10.1182/blood-2014-11-612416 | DOI Listing |
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