ArticlePloS one2012
H2O2 production downstream of FLT3 is mediated by p22phox in the endoplasmic reticulum and is required for STAT5 signalling.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 58 citations in OpenAlex.
- Intracellular Oxidant Levels Are Crucial for Cell Survival and JAK/STAT Signaling in Classical Hodgkin's Lymphoma.Antioxidants (Basel, Switzerland) · 2026Article
- Metabolic Signature ofJournal of personalized medicine · 2025Review
- DNA damage accumulation and repair defects in FLT3-ITD acute myeloid leukemia: Implications for clonal evolution and disease progression.Hematological oncology · 2023Review
- Sodium activates human monocytes via the NADPH oxidase and isolevuglandin formation.Cardiovascular research · 2021Article
- Characterization of NADPH Oxidase Expression and Activity in Acute Myeloid Leukemia Cell Lines: A Correlation with the Differentiation Status.Antioxidants (Basel, Switzerland) · 2021Article
- The multifaceted role of reactive oxygen species in tumorigenesis.Cellular and molecular life sciences : CMLS · 2020Review
- Chemical Composition and Immunomodulatory Activity ofBiomolecules · 2020Article
- Pharmacological Inhibition of Oncogenic STAT3 and STAT5 Signaling in Hematopoietic Cancers.Cancers · 2020Review
- The Role of Reactive Oxygen Species in Acute Myeloid Leukaemia.International journal of molecular sciences · 2019Review
- Hematopoietic Stem Cells: Normal Versus Malignant.Antioxidants & redox signaling · 2018Review
- The Cooperative Relationship between STAT5 and Reactive Oxygen Species in Leukemia: Mechanism and Therapeutic Potential.Cancers · 2018Review
- Recent Developments in the Probes and Assays for Measurement of the Activity of NADPH Oxidases.Cell biochemistry and biophysics · 2017Article
- Nuclear membrane-localised NOX4D generates pro-survival ROS in FLT3-ITD-expressing AML.Oncotarget · 2017Article
- How do we fit ferroptosis in the family of regulated cell death?Cell death and differentiation · 2017Review
- Imipramine blue sensitively and selectively targets FLT3-ITD positive acute myeloid leukemia cells.Scientific reports · 2017Article
- Excessive Reactive Oxygen Species and Exotic DNA Lesions as an Exploitable Liability.Biochemistry · 2016Review
- NOX4-driven ROS formation mediates PTP inactivation and cell transformation in FLT3ITD-positive AML cells.Leukemia · 2016Article
- NADPH oxidase-generated hydrogen peroxide induces DNA damage in mutant FLT3-expressing leukemia cells.The Journal of biological chemistry · 2015Article
- Oxidative stress, bone marrow failure, and genome instability in hematopoietic stem cells.International journal of molecular sciences · 2015Review
- Nox NADPH oxidases and the endoplasmic reticulum.Antioxidants & redox signaling · 2014Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
The internal tandem duplication (ITD) of the juxtamembrane region of the FLT3 receptor has been associated with increased reactive oxygen species (ROS) generation in acute myeloid leukemia (AML). How this elevated level of ROS contributes to the leukemic phenotype, however, remains poorly understood. In this work we show that ROS in the FLT3-ITD expressing AML cell line MV4-11 is reduced by treatment with PKC412, an inhibitor of FLT3, DPI, a flavoprotein inhibitor, and VAS2870, a Nox specific inhibitor, suggesting that ROS production is both FLT3 and NADPH oxidase dependent. The majority of these ROS co-localize to the endoplasmic reticulum (ER), as determined with the H(2)O(2)-specific aryl-boronate dye Peroxyorange 1, which also corresponds to co-localization of p22phox. Moreover, knocking down p22phox dramatically reduces H(2)O(2) after 24 hours in the ER, without affecting mitochondrial ROS. Significantly, the FLT3 inhibitor PKC412 reduces H(2)O(2) in FLT3-ITD expressing cell lines (MV4-11, MOLM-13) through reduction of p22phox over 24 hours. Reduced p22phox is achieved by proteasomal degradation and is prevented upon GSK3-β inhibition. Knockdown of p22phox resulted in reduced STAT5 signalling and reduced Pim-1 levels in the cells after 24 hours. Thus, we have shown that FLT3 driven H(2)O(2) production in AML cells is mediated by p22phox and is critical for STAT5 signalling.
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Registered trials
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