New insights into redox homeostasis as a therapeutic target in B-cell malignancies

Curr Opin Hematol. 2017 Jul;24(4):393-401. doi: 10.1097/MOH.0000000000000351.


Purpose of review: 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.

Recent findings: 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.

Summary: 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.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Antioxidants / metabolism
  • Cell Communication
  • Clinical Studies as Topic
  • Drug Evaluation, Preclinical
  • Drug Synergism
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Homeostasis*
  • Humans
  • Leukemia, B-Cell / drug therapy
  • Leukemia, B-Cell / genetics
  • Leukemia, B-Cell / metabolism*
  • Lymphoma, B-Cell / drug therapy
  • Lymphoma, B-Cell / genetics
  • Lymphoma, B-Cell / metabolism*
  • Metabolic Networks and Pathways
  • Oxidation-Reduction* / drug effects
  • Oxidative Stress / drug effects
  • Reactive Oxygen Species / metabolism
  • Signal Transduction


  • Antineoplastic Agents
  • Antioxidants
  • Reactive Oxygen Species