Dataset Information

CROSsing the Line: Between Beneficial and Harmful Effects of Reactive Oxygen Species in B-Cell Malignancies.

ABSTRACT: B-cell malignancies are a heterogeneous group of hematological neoplasms derived from cells at different stages of B-cell development. Recent studies revealed that dysregulated redox metabolism is one of the factors contributing to the pathogenesis and progression of B-cell malignancies. Elevated levels of oxidative stress markers usually correlate with the advanced stage of various B-cell malignancies. In the complex tumor microenvironment, reactive oxygen species affect not only malignant cells but also bystander cells, including immune cells. Importantly, malignant cells, due to genetic dysregulation, are able to adapt to the increased demands for energy and reducing equivalents via metabolic reprogramming and upregulation of antioxidants. The immune cells, however, are more sensitive to oxidative imbalance. This may cause their dysfunction, leading to immune evasion and tumor progression. On the other hand, the already imbalanced redox homeostasis renders malignant B-cells particularly sensitive to further elevation of reactive oxygen species. Indeed, targeting antioxidant systems has already presented anti-leukemic efficacy in preclinical models. Moreover, the prooxidant treatment that triggers immunogenic cell death has been utilized to generate autologous anti-leukemic vaccines. In this article, we review novel research on the dual role of the reactive oxygen species in B-cell malignancies. We highlight the mechanisms of maintaining redox homeostasis by malignant B-cells along with the antioxidant shield provided by the microenvironment. We summarize current findings regarding therapeutic targeting of redox metabolism in B-cell malignancies. We also discuss how the oxidative stress affects antitumor immune response and how excessive reactive oxygens species influence anticancer prooxidant treatments and immunotherapies.

SUBMITTER: Domka K

PROVIDER: S-EPMC7385186 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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cROSsing the Line: Between Beneficial and Harmful Effects of Reactive Oxygen Species in B-Cell Malignancies.

Domka Krzysztof K Goral Agnieszka A Firczuk Malgorzata M

Frontiers in immunology 20200721

B-cell malignancies are a heterogeneous group of hematological neoplasms derived from cells at different stages of B-cell development. Recent studies revealed that dysregulated redox metabolism is one of the factors contributing to the pathogenesis and progression of B-cell malignancies. Elevated levels of oxidative stress markers usually correlate with the advanced stage of various B-cell malignancies. In the complex tumor microenvironment, reactive oxygen species affect not only malignant cell ...[more]

PMID: 32793211

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Project description:Wollbold2014 - Effects of reactive oxygen species This model is described in the article: Anti-inflammatory effects of reactive oxygen species ¿ a multi-valued logical model validated by formal concept analysis. Wollbold J, Jaster R, Müller S, Rateitschak K, Wolkenhauer O. BMC Syst Biol 2014 Sep; 8(1): 101 Abstract: BackgroundRecent findings suggest that in pancreatic acinar cells stimulated with bile acid, a pro-apoptotic effect of reactive oxygen species (ROS) dominates their effect on necrosis and spreading of inflammation. The first effect presumably occurs via cytochrome C release from the inner mitochondrial membrane. A pro-necrotic effect ¿ similar to the one of Ca2+ ¿ can be strong opening of mitochondrial pores leading to breakdown of the membrane potential, ATP depletion, sustained Ca2+ increase and premature activation of digestive enzymes. To explain published data and to understand ROS effects during the onset of acute pancreatitis, a model using multi-valued logic is constructed. Formal concept analysis (FCA) is used to validate the model against data as well as to analyze and visualize rules that capture the dynamics.ResultsSimulations for two different levels of bile stimulation and for inhibition or addition of antioxidants reproduce the qualitative behaviour shown in the experiments. Based on reported differences of ROS production and of ROS induced pore opening, the model predicts a more uniform apoptosis/necrosis ratio for higher and lower bile stimulation in liver cells than in pancreatic acinar cells. FCA confirms that essential dynamical features of the data are captured by the model. For instance, high necrosis always occurs together with at least a medium level of apoptosis. At the same time, FCA helps to reveal subtle differences between data and simulations. The FCA visualization underlines the protective role of ROS against necrosis.ConclusionsThe analysis of the model demonstrates how ROS and decreased antioxidant levels contribute to apoptosis. Studying the induction of necrosis via a sustained Ca2+ increase, we implemented the commonly accepted hypothesis of ATP depletion after strong bile stimulation. Using an alternative model, we demonstrate that this process is not necessary to generate the dynamics of the measured variables. Opening of plasma membrane channels could also lead to a prolonged increase of Ca2+ and to necrosis. Finally, the analysis of the model suggests a direct experimental testing for the model-based hypothesis of a self-enhancing cycle of cytochrome C release and ROS production by interruption of the mitochondrial electron transport chain. This model is hosted on BioModels Database and identified by: MODEL1407230001. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Dataset Information

CROSsing the Line: Between Beneficial and Harmful Effects of Reactive Oxygen Species in B-Cell Malignancies.

Publications

cROSsing the Line: Between Beneficial and Harmful Effects of Reactive Oxygen Species in B-Cell Malignancies.

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