NOX-driven ROS formation in cell transformation of FLT3-ITD positive AML

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dc.contributor.author Jayavelu, Ashok K.
dc.contributor.author Moloney, Jennifer N.
dc.contributor.author Böhmer, Frank D.
dc.contributor.author Cotter, Thomas G.
dc.date.accessioned 2016-10-03T10:27:46Z
dc.date.available 2016-10-03T10:27:46Z
dc.date.issued 2016-09-22
dc.identifier.citation Jayavelu, A. K., Moloney, J. N., Böhmer, F.-D. & Cotter, T. G. ‘NOX-driven ROS formation in cell transformation of FLT3-ITD positive AML’, Experimental Hematology. In Press. en
dc.identifier.issn 0301-472X
dc.identifier.issn 1873-2399
dc.identifier.uri http://hdl.handle.net/10468/3148
dc.identifier.doi 10.1016/j.exphem.2016.08.008
dc.description.abstract In different types of myeloid leukemia, increased formation of reactive oxygen species (ROS) has been noted and associated with aspects of cell transformation including the promotion of leukemic cell proliferation and migration, as well as DNA-damage and accumulation of mutations. Work reviewed in this article has shown the involvement of NADPH oxidase (NOX)-derived ROS downstream of oncogenic protein-tyrosine kinases in both processes, and the related pathways have been partially identified. FLT3-ITD, an important oncoprotein in a subset of AML, causes activation of AKT and subsequently stabilization of p22phox, a regulatory subunit for NOX1-4. This process is linked to ROS formation and DNA damage. Moreover, FLT3-ITD signaling through STAT5 enhances expression of NOX4, ROS formation and inactivation of the protein-tyrosine phosphatase DEP-1/PTPRJ, a negative regulator of FLT3 signaling, by reversible oxidation of its catalytic cysteine residue. Genetic inactivation of NOX4 restored DEP-1 activity and attenuated cell transformation by FLT3-ITD in vitro and in vivo. Future work is required to further explore these mechanisms and their causal involvement in leukemic cell transformation, which may result in the identification of novel candidate targets for therapy. en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Elsevier en
dc.rights © Elsevier 2016. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ en
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/ en
dc.subject PTP oxidation en
dc.subject Protein-tyrosine phosphatase (PTP) en
dc.subject DNA damage en
dc.subject FLT3-ITD en
dc.subject AML en
dc.subject Reactive oxygen species en
dc.subject Myeloid leukemia en
dc.title NOX-driven ROS formation in cell transformation of FLT3-ITD positive AML en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Thomas Cotter, Biochemistry & Cell Biology, University College Cork, Cork, Ireland. +353-21-490-3000 Email: t.cotter@ucc.ie en
dc.internal.availability Full text available en
dc.check.info 12 month embargo at publisher's request en
dc.check.date 2017-09-22
dc.description.version Accepted Version en
dc.description.status Peer reviewed en
dc.identifier.journaltitle Experimental Hematology en
dc.internal.copyrightchecked !!CORA!! en
dc.internal.IRISemailaddress t.cotter@ucc.ie en
dc.internal.bibliocheck Article In Press. 22 Sept 2016 en


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© Elsevier 2016. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ Except where otherwise noted, this item's license is described as © Elsevier 2016. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
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