title: New insights into redox homeostasis as a therapeutic target in B-cell malignancies.
abstract: OBJECTIVE
  The goal of this review is to summarize recent advances in our understanding of the regulation of redox homeostasis and the subtype-specific role of antioxidant enzymes in B-cell-derived malignancies. Furthermore, it presents selected prooxidative therapeutic strategies against B-cell neoplasms.
  
  
  RESULTS
  Recent reports have shown that the disturbed redox homeostasis in B-cell malignancies is regulated by cancer-specific signaling pathways and therefore varies between the individual subtypes. For instance, in a subtype of diffuse large B-cell lymphoma with increased oxidative phosphorylation, elevated reactive oxygen species are accompanied by higher levels of thioredoxin and glutathione and inhibition of either of these systems is selectively toxic to this subtype. In addition, growing number of small molecule inhibitors targeting antioxidant enzymes, such as auranofin, SK053, adenanthin, or decreasing glutathione level, such as imexon, buthionine sulfoximine, and L-cysteinase, trigger specific cytotoxic effects against B-cell malignancies. Lastly, attention is drawn to recent reports of effective treatment modalities involving prooxidative agents and interfering with redox homeostasis provided by stromal cells.
  
  
  CONCLUSIONS
  Recent findings reveal important differences in redox homeostasis within the distinct subsets of B-cell-derived malignancies that can be therapeutically exploited to improve existing treatment and to overcome drug resistance.
authors.affiliation: aDepartment of Immunology, Center for Biostructure Research, Medical University of Warsaw bDepartment of Clinical Immunology, Transplantation Institute, Medical University of Warsaw cDepartment of Bioinformatics, Institute of Biochemistry and Biophysics, Polish Academy of Sciences dPostgraduate School of Molecular Medicine, Medical University of Warsaw eInstitute of Hematology and Transfusion Medicine, Warsaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Graczyk-Jarzynka
authors.forename: Radoslaw
authors.initials: R
authors.lastname: Zagozdzon
authors.forename: Angelika
authors.initials: A
authors.lastname: Muchowicz
authors.forename: Marta
authors.initials: M
authors.lastname: Siernicka
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Juszczynski
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Firczuk
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000975:Antioxidants / Q000378:metabolism; D002450:Cell Communication; D000068456:Clinical Studies as Topic; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006706:Homeostasis; D006801:Humans; D015448:Leukemia, B-Cell / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D053858:Metabolic Networks and Pathways; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D017382:Reactive Oxygen Species