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Review
. 2024:164:1-68.
doi: 10.1016/bs.acr.2024.04.008. Epub 2024 May 14.

Redox, cysteines, and kinases-A triad sustaining myeloid leukemia

Vanessa Marensi  1
Affiliations
Review

Redox, cysteines, and kinases-A triad sustaining myeloid leukemia

Vanessa Marensi. Adv Cancer Res. 2024.

Abstract

Reactive oxygen species (ROS) work as a second messenger, modulating cell response and establishing homeostasis. Abrupt changes in ROS are used to modulate transient cell response to different stimuli, from viral infection to inflammation. Chronic exposure to high ROS concentration can cause cellular damage and promote the development of diseases. Leukemogenesis is adapted to high concentrations of ROS, hijacking the ROS system, and uses kinase cascades to promote survival advantages. The oxidation-reduction (redox) machinery is composed of enzymes that orchestrate all classes of protein and use available Cys as transmitters and sensors, to disseminate stress signals through cells via kinase cascades. Myeloid leukemias (MLs) are known for being a heterogeneous disease, and clonal diversity is remarkably characterized by differences in the activation of kinase-regulated signaling cascades to provide survival advantage. Stress-activated kinase cascades and other cascades are regulated by the ROS system. Several studies present nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) and the ER-resident NOX4 as key elements of ROS activity in healthy myeloid cells and myeloid leukemia. Targeting ROS presents an attractive therapeutic strategy for (MLs) patients, but the boundaries between pro-apoptotic and anti-apoptotic ROS concentrations are not well established. Detailed understanding of the signaling switches that determine cell fate needs to be well understood. This work explores several aspects of the redox system and thiol-mediated reactions with focus on kinase signaling in myeloid cancers and highlights some of the challenges.

Keywords: Cysteines; Kinases; Myeloid leukemia; Post-translational modification; Reactive oxygen species; Redox.

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