Protein Phosphorylation and Redox Status: An as Yet Elusive Dyad in Chronic Lymphocytic Leukemia

• Published in: Cancers 2022-10, Vol.14 (19), p.4881
• Main Authors: Pagano, Mario Angelo, Frezzato, Federica, Visentin, Andrea, Trentin, Livio, Brunati, Anna Maria
• Format: Article
• Language: English
• Subjects: Antioxidants; Bone marrow; By products; Chronic lymphocytic leukemia; Development and progression; Drug development; Enzymes; Glutathione; Health aspects; Homeostasis; Isoforms; Kinases; Leukemia; Ligands; Lipids; Lymph nodes; Lymphoid tissue; Metabolism; Microenvironments; Mitochondria; Oxidation-reduction reaction; Oxidative phosphorylation; Oxidative stress; Pathogenesis; Phenotypes; Phosphatase; Phosphorylation; Physiology; Proteins; Reactive oxygen species; Review; Superoxide dismutase; Synergism; Thioredoxin; Transcription activation; Transcription factors
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers14194881

Malignant cells in chronic lymphocytic leukemia (CLL) are characterized by oxidative stress that is related to abundant generation of reactive oxygen species (ROS) by increased mitochondrial oxidative phosphorylation (OXPHOS). Lymphoid tissues have been shown to provide a protective microenvironment that antagonizes the effects of ROS, contributing to establishing redox homeostasis that supports the vitality of CLL cells. In the last few decades, a complex antioxidant machinery has been demonstrated to be activated in CLL cells, including the different superoxide dismutase (SOD) isoforms, the thioredoxin (Trx) system, and the enzyme cascade inducing glutathione (GSH) biosynthesis and recycling, to name a few. Their expression is known to be upregulated by the activation of specific transcription factors, which can be regulated by either oxidative stress or phosphorylation. These two latter aspects have mostly been explored separately, and only recently an increasing body of evidence has been providing reasonable inference that ROS and phosphorylation may cooperate in an interplay that contributes to the survival mechanisms of CLL cells. Here, we present an overview of how oxidative stress and phosphorylation-dependent signals are intertwined in CLL, focusing on transcription factors that regulate the balance between ROS production and scavenging.