| Literature DB >> 34027418 |
Anca Franzini1, Anthony D Pomicter1, Dongqing Yan1, Brayden J Halverson1, Orlando Antelope1, Clinton C Mason2, Jonathan M Ahmann1, Anna V Senina1, Nadeem A Vellore1, Courtney L Jones3, Matthew S Zabriskie1, Hein Than4, Michael J Xiao1, Alexandria van Scoyk1, Ami B Patel5, Phillip M Clair1, William L Heaton1, Shawn C Owen6, Joshua L Andersen7, Christina M Egbert7, Julie A Reisz8, Angelo D'Alessandro3,8, James E Cox9, Kevin C Gantz1, Hannah M Redwine1, Siddharth M Iyer1, Jamshid S Khorashad10, Nima Rajabi11, Christian A Olsen11, Thomas O'Hare1,5, Michael W Deininger12,5.
Abstract
We discovered that the survival and growth of many primary acute myeloid leukemia (AML) samples and cell lines, but not normal CD34+ cells, are dependent on SIRT5, a lysine deacylase implicated in regulating multiple metabolic pathways. Dependence on SIRT5 is genotype-agnostic and extends to RAS- and p53-mutated AML. Results were comparable between SIRT5 knockdown and SIRT5 inhibition using NRD167, a potent and selective SIRT5 inhibitor. Apoptosis induced by SIRT5 disruption is preceded by reductions in oxidative phosphorylation and glutamine utilization, and an increase in mitochondrial superoxide that is attenuated by ectopic superoxide dismutase 2. These data indicate that SIRT5 controls and coordinates several key metabolic pathways in AML and implicate SIRT5 as a vulnerability in AML.Entities:
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Year: 2019 PMID： 34027418 PMCID： PMC8133360 DOI： 10.1158/2643-3230.BCD-20-0168
Source DB: PubMed Journal: Blood Cancer Discov ISSN： 2643-3230