Targeting Redox Regulation as a Therapeutic Opportunity against Acute Leukemia: Pro-Oxidant Strategy or Antioxidant Approach?

Redox adaptation is essential for human health, as the physiological quantities of non-radical reactive oxygen species operate as the main second messengers to regulate normal redox reactions by controlling several sensors. An abnormal increase reactive oxygen species, called oxidative stress, induc...

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Main Authors: Alessandro Allegra, Alessandro Tonacci, Laura Giordano, Caterina Musolino, Sebastiano Gangemi
Format: Article
Language:English
Published: MDPI AG 2022-08-01
Series:Antioxidants
Subjects:
Online Access:https://www.mdpi.com/2076-3921/11/9/1696
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author Alessandro Allegra
Alessandro Tonacci
Laura Giordano
Caterina Musolino
Sebastiano Gangemi
author_facet Alessandro Allegra
Alessandro Tonacci
Laura Giordano
Caterina Musolino
Sebastiano Gangemi
author_sort Alessandro Allegra
collection DOAJ
description Redox adaptation is essential for human health, as the physiological quantities of non-radical reactive oxygen species operate as the main second messengers to regulate normal redox reactions by controlling several sensors. An abnormal increase reactive oxygen species, called oxidative stress, induces biological injury. For this reason, variations in oxidative stress continue to receive consideration as a possible approach to treat leukemic diseases. However, the intricacy of redox reactions and their effects might be a relevant obstacle; consequently, and alongside approaches aimed at increasing oxidative stress in neoplastic cells, antioxidant strategies have also been suggested for the same purpose. The present review focuses on the molecular processes of anomalous oxidative stress in acute myeloid and acute lymphoblastic leukemias as well as on the oxidative stress-determined pathways implicated in leukemogenic development. Furthermore, we review the effect of chemotherapies on oxidative stress and the possibility that their pharmacological effects might be increased by modifying the intracellular redox equilibrium through a pro-oxidant approach or an antioxidant strategy. Finally, we evaluated the prospect of varying oxidative stress as an efficacious modality to destroy chemoresistant cells using new methodologies. Altering redox conditions may be advantageous for inhibiting genomic variability and the eradication of leukemic clones will promote the treatment of leukemic disease.
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spelling doaj.art-08101d0c45774bb9ad604d79ccafab932023-11-23T14:47:25ZengMDPI AGAntioxidants2076-39212022-08-01119169610.3390/antiox11091696Targeting Redox Regulation as a Therapeutic Opportunity against Acute Leukemia: Pro-Oxidant Strategy or Antioxidant Approach?Alessandro Allegra0Alessandro Tonacci1Laura Giordano2Caterina Musolino3Sebastiano Gangemi4Division of Hematology, Department of Human Pathology in Adulthood and Childhood “Gaetano Barresi”, University of Messina, 98125 Messina, ItalyClinical Physiology Institute, National Research Council of Italy (IFC-CNR), 56124 Pisa, ItalyDivision of Hematology, Department of Human Pathology in Adulthood and Childhood “Gaetano Barresi”, University of Messina, 98125 Messina, ItalyDivision of Hematology, Department of Human Pathology in Adulthood and Childhood “Gaetano Barresi”, University of Messina, 98125 Messina, ItalyAllergy and Clinical Immunology Unit, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, ItalyRedox adaptation is essential for human health, as the physiological quantities of non-radical reactive oxygen species operate as the main second messengers to regulate normal redox reactions by controlling several sensors. An abnormal increase reactive oxygen species, called oxidative stress, induces biological injury. For this reason, variations in oxidative stress continue to receive consideration as a possible approach to treat leukemic diseases. However, the intricacy of redox reactions and their effects might be a relevant obstacle; consequently, and alongside approaches aimed at increasing oxidative stress in neoplastic cells, antioxidant strategies have also been suggested for the same purpose. The present review focuses on the molecular processes of anomalous oxidative stress in acute myeloid and acute lymphoblastic leukemias as well as on the oxidative stress-determined pathways implicated in leukemogenic development. Furthermore, we review the effect of chemotherapies on oxidative stress and the possibility that their pharmacological effects might be increased by modifying the intracellular redox equilibrium through a pro-oxidant approach or an antioxidant strategy. Finally, we evaluated the prospect of varying oxidative stress as an efficacious modality to destroy chemoresistant cells using new methodologies. Altering redox conditions may be advantageous for inhibiting genomic variability and the eradication of leukemic clones will promote the treatment of leukemic disease.https://www.mdpi.com/2076-3921/11/9/1696oxidative stressacute myeloid leukemiaacute lymphoblastic leukemiareactive oxygen speciesmitochondria
spellingShingle Alessandro Allegra
Alessandro Tonacci
Laura Giordano
Caterina Musolino
Sebastiano Gangemi
Targeting Redox Regulation as a Therapeutic Opportunity against Acute Leukemia: Pro-Oxidant Strategy or Antioxidant Approach?
Antioxidants
oxidative stress
acute myeloid leukemia
acute lymphoblastic leukemia
reactive oxygen species
mitochondria
title Targeting Redox Regulation as a Therapeutic Opportunity against Acute Leukemia: Pro-Oxidant Strategy or Antioxidant Approach?
title_full Targeting Redox Regulation as a Therapeutic Opportunity against Acute Leukemia: Pro-Oxidant Strategy or Antioxidant Approach?
title_fullStr Targeting Redox Regulation as a Therapeutic Opportunity against Acute Leukemia: Pro-Oxidant Strategy or Antioxidant Approach?
title_full_unstemmed Targeting Redox Regulation as a Therapeutic Opportunity against Acute Leukemia: Pro-Oxidant Strategy or Antioxidant Approach?
title_short Targeting Redox Regulation as a Therapeutic Opportunity against Acute Leukemia: Pro-Oxidant Strategy or Antioxidant Approach?
title_sort targeting redox regulation as a therapeutic opportunity against acute leukemia pro oxidant strategy or antioxidant approach
topic oxidative stress
acute myeloid leukemia
acute lymphoblastic leukemia
reactive oxygen species
mitochondria
url https://www.mdpi.com/2076-3921/11/9/1696
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