2015
DOI: 10.1074/jbc.m113.510495
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NADPH Oxidase-generated Hydrogen Peroxide Induces DNA Damage in Mutant FLT3-expressing Leukemia Cells

Abstract: Background: NADPH oxidase is a hydrogen peroxide-generating enzyme, involved in redox signaling in cancer. Results: NADPH oxidase-generated hydrogen peroxide increases DNA damage and genomic instability. Conclusion: NADPH oxidase-derived hydrogen peroxide mediates DNA damage in acute myeloid leukemia (AML). Significance: The mechanism of DNA damage generation is important for studying aggressive AML phenotypes.

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Cited by 85 publications
(92 citation statements)
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“…It will thus be important to test FLT3 inhibitors in combination with MTH FD2 suppression in future studies. Although the precise mechanism for increased sensitivity to MTH FD2 suppression in FLT3-ITD AML is uncertain, one might speculate that the increased production of reactive oxygen species by internal tandem duplications of FLT3 may render greater sensitivity (Sallmyr et al, 2008;Godfrey et al, 2012;Stanicka et al, 2015).…”
Section: Discussionmentioning
confidence: 99%
“…It will thus be important to test FLT3 inhibitors in combination with MTH FD2 suppression in future studies. Although the precise mechanism for increased sensitivity to MTH FD2 suppression in FLT3-ITD AML is uncertain, one might speculate that the increased production of reactive oxygen species by internal tandem duplications of FLT3 may render greater sensitivity (Sallmyr et al, 2008;Godfrey et al, 2012;Stanicka et al, 2015).…”
Section: Discussionmentioning
confidence: 99%
“…Emerald 1 (NucPE1). NOX4 and p22 phox were shown to co-localize in the nucleus, thus reinforcing that nuclear NOX activity may contribute to genomic instability in AML [26]. FLT3-ITD expressing 32D cells exhibited a 100% increase in endogenous H 2 O 2 compared to FLT-WT expressing cells as quantified by flow cytometry using the H 2 O 2 specific probe Peroxy Orange 1 (PO1), and a 25% increase in nuclear H 2 O 2 .…”
Section: A C C E P T E D Accepted Manuscriptmentioning
confidence: 98%
“…and their partner protein p22 phox compared to wild type FLT3 cells [26,28]. Also, stimulation of The enhanced ROS formation in FLT3-ITD expressing AML cells serves a signaling function in that it promotes cell proliferation and migration, and thereby contributes to leukemic cell transformation [21,27].…”
Section: A C C E P T E D Accepted Manuscriptmentioning
confidence: 99%
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