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

Advances in cancer research Pub Date : 2024-01-01 Epub Date: 2024-05-14 DOI:10.1016/bs.acr.2024.04.008
Vanessa Marensi
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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.

氧化还原、半胱氨酸和激酶--维持骨髓性白血病的三要素。
活性氧(ROS)作为第二信使起着调节细胞反应和建立平衡的作用。从病毒感染到炎症,ROS 的突然变化可用于调节细胞对不同刺激的短暂反应。长期暴露于高浓度的 ROS 会造成细胞损伤,促进疾病的发展。白细胞生成适应高浓度的 ROS,劫持 ROS 系统,利用激酶级联促进生存优势。氧化还原(Redox)机制由各种酶组成,它们协调各类蛋白质,利用可用的 Cys 作为发射器和传感器,通过激酶级联在细胞中传播应激信号。众所周知,骨髓性白血病(MLs)是一种异质性疾病,克隆多样性的显著特点是激活激酶调控的信号级联以提供生存优势方面的差异。应激活化激酶级联和其他级联受 ROS 系统调控。多项研究表明,烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶 2(NOX2)和 ER 驻留型 NOX4 是健康髓系细胞和髓系白血病中 ROS 活性的关键因素。针对 ROS 的治疗策略对髓性白血病患者很有吸引力,但促凋亡 ROS 浓度和抗凋亡 ROS 浓度之间的界限尚未明确。我们需要深入了解决定细胞命运的信号转导开关。这项研究探讨了氧化还原系统和硫醇介导反应的几个方面,重点是骨髓癌中的激酶信号转导,并强调了其中的一些挑战。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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