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Acute myelogenous leukemia (AML)

Glutamate-cysteine ligase catalytic subunit (GCLC); glutathione peroxidase 1 (GPX1)

In vitro studies suggest inhibiting glutathione metabolism could help treat AML. In CD34+ leukemia stem cells, compared with normal CD34+ hematopoietic cells, levels of both glutathione pathway regulatory proteins and oxidized glutathione were increased. In the leukemia stem cells, the natural products parthenolide and piperlongumine, which inhibit glutathione metabolism targets including GCLC and GPX1, depleted glutathione and induced cell death when given as monotherapy. In primary AML specimens, cytarabine plus parthenolide synergistically induced cell death. Next steps could include testing glutathione metabolism inhibitors in animal models of AML.

SciBX 6(45); doi:10.1038/scibx.2013.1284
Published online Nov. 21, 2013

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Pei, S. et al. J. Biol. Chem.;
published online Oct. 2, 2013;
Contact: Craig T. Jordan,
University of Colorado Denver, Aurora, Co.