A mechanism for increased sensitivity of acute myeloid leukemia to mitotoxic drugs

Simple item page
dc.citation.articleNumber617en_US
dc.citation.journalTitleCell Death & Diseaseen_US
dc.citation.volumeNumber10en_US
dc.contributor.authorPanina, Svetlana B.en_US
dc.contributor.authorBaran, Nataliaen_US
dc.contributor.authorda Costa, Fabio H.Brasilen_US
dc.contributor.authorKonopleva, Marinaen_US
dc.contributor.authorKirienko, Natalia V.en_US
dc.date.accessioned2019-11-14T17:52:26Zen_US
dc.date.available2019-11-14T17:52:26Zen_US
dc.date.issued2019en_US
dc.description.abstractMitochondria play a central and multifunctional role in the progression of tumorigenesis. Although many recent studies have demonstrated correlations between mitochondrial function and genetic makeup or originating tissue, it remains unclear why some cancers are more susceptible to mitocans (anticancer drugs that target mitochondrial function to mediate part or all of their effect). Moreover, fundamental questions of efficacy and mechanism of action in various tumor types stubbornly remain. Here we demonstrate that cancer type is a significant predictor of tumor response to mitocan treatment, and that acute myeloid leukemias (AML) show an increased sensitivity to these drugs. We determined that AML cells display particular defects in mitochondrial metabolism that underlie their sensitivity to mitocan treatment. Furthermore, we demonstrated that combinatorial treatment with a mitocan (CCCP) and a glycolytic inhibitor (2-deoxyglucose) has substantial synergy in AML cells, including primary cells from patients with AML. Our results show that mitocans, either alone or in combination with a glycolytic inhibitor, display anti-leukemia effects in doses much lower than needed to induce toxicity against normal blood cells, indicating that mitochondria may be an effective and selective therapeutic target.en_US
dc.identifier.citationPanina, Svetlana B., Baran, Natalia, da Costa, Fabio H.Brasil, et al.. "A mechanism for increased sensitivity of acute myeloid leukemia to mitotoxic drugs." <i>Cell Death & Disease,</i> 10, (2019) Springer Nature: https://doi.org/10.1038/s41419-019-1851-3.en_US
dc.identifier.digitalmechanism-increased-sensitivityen_US
dc.identifier.doihttps://doi.org/10.1038/s41419-019-1851-3en_US
dc.identifier.urihttps://hdl.handle.net/1911/107685en_US
dc.language.isoengen_US
dc.publisherSpringer Natureen_US
dc.rightsThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleA mechanism for increased sensitivity of acute myeloid leukemia to mitotoxic drugsen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
mechanism-increased-sensitivity.pdf
Size:
2.27 MB
Format:
Adobe Portable Document Format
Download
Collections
Faculty Publications
BioSciences Publications