Overview of thioredoxin system and targeted therapies for acute leukemia

Xie, Weiling; Ma, Weijie; Liu, Pan; Zhou, Fuling

doi:10.1016/j.mito.2019.04.010

Cited by 29 publications

(22 citation statements)

References 76 publications

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“…Anti-infection, liver protection, jaundice alleviation, and low molecular weight heparin can be offered to improve the prognosis of children. [ 23 ] In terms of preventing the recurrence of ALL in children, 6-TG may be more effective than 6-MP, but 6-TG has strong hepatotoxicity, which should be avoided to use for in the long run. Ongoing pharmacogenetic studies can establish models to explore whether children with specific type can benefit from 6-TG.…”

Section: Discussionmentioning

confidence: 99%

Clinical efficacy and safety of 6-thioguanine in the treatment of childhood acute lymphoblastic leukemia

et al. 2020

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Background: To systematic review the efficacy and safety of 6-thioguanine (6-TG) in the substitute of 6-mercaptopurine (6-MP) in the treatment for patients with childhood acute lymphoblastic leukemia (ALL) in the maintenance phase, and to explore its clinical application value. It provides theoretical guidance for the maintenance treatment of ALL in children from the perspective of evidence-based medicine. Methods: By means of computer retrieval, Chinese databases were searched: Chinese Biomedical Database (CBM), China national knowledge internet (CNKI), Chongqing Weipu Database (VIP), and Wanfang Database; Foreign databases: PubMed, The Cochrane Library, Embase, and Web of Science were applied to find out randomized controlled trial (RCT) for 6-TG in childhood acute lymphoblastic leukemia. By manual retrieval, documents without electronic edition and related conference papers were retrieved. The retrieval time ranges from the beginning of the establishment of the databases to September 1st, 2019. According to the inclusion, and exclusion criteria by 3 researchers, the literature screening, data extraction, and research methodological quality evaluation were completed. RevMan 5.3 software was applied to evaluate the quality of the included literature, and Stata 12.0 software was used to conduct meta-analysis of the outcome indicators of the included literature. Results: This study systematically evaluated the efficacy and safety of 6-TG in the substitute of 6-MP as a maintenance drug for childhood acute lymphoblastic leukemia. Through the key outcome indicators, this study is expected to draw a scientific, practical conclusion for 6-TG in the treatment of childhood acute lymphoblastic leukemia. This conclusion will provide evidence-based medical direction for clinical treatment. Conclusion: The efficacy and safety of 6-TG in the substitute of 6-MP in the maintenance treatment of childhood acute lymphoblastic leukemia will be confirmed through this study. The conclusions will be published in relevant academic journals. Registration: PROSPERO (registration number is CRD42020150466).

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Section: Discussionmentioning

confidence: 99%

Clinical efficacy and safety of 6-thioguanine in the treatment of childhood acute lymphoblastic leukemia

et al. 2020

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“…Peroxiredoxin reduces hydrogen peroxide, and the oxidized peroxiredoxin is, in turn, reduced by Trx. Furthermore, oxidized Trx is recycled by thioredoxin reductase using NADPH [79]. In the presence of thioredoxin reductase, Trx takes electrons from NADP H, transfers them to the active site of Trx, then uses the electrons to decrease protein disulfides [80].…”

Section: Cellular Antioxidants In Myeloid Leukemiamentioning

confidence: 99%

The significant role of redox system in myeloid leukemia: from pathogenesis to therapeutic applications

et al. 2020

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Background Excessive generation of reactive oxygen species (ROS) in the presence of a defective antioxidant system can induce cellular damage and disrupt normal physiological functions. Several studies have revealed the unfavorable role of ROS in promoting the growth, proliferation, migration, and survival of leukemia cells. In this review study, we summarize the mechanisms of ROS production and its role in leukemogenesis, counteractive effects of antioxidants, and implicate the current ROS-dependent anticancer therapies in acute myeloid leukemia. Body The dysregulation of the redox system is known to play a significant role in the pathogenesis of leukemia. Leukemia cells generate high levels of ROS, which further increases the levels through extra pathways, including mitochondrial deoxyribonucleic mutation, leukemic oncogene activation, increased nicotinamide adenine phosphate hydrogen (NADPH), and cytochrome P450 activities. Aforementioned pathways once activated have shown to promote genomic instability, induce drug resistance to leukemia medical therapy, disease relapse and reduce survival period. The current standard of treatment with chemotherapy employs the pro-oxidant approach to induce apoptosis and promote tumor regression. However, this approach retains several deleterious effects on the subject resulting in degradation of the quality of life. Nevertheless, the addition of an antioxidant as an adjuvant drug to chemotherapy alleviates treatment-related toxicity, increases chemotherapeutic efficacy, and improves survival rates of a patient. Conclusion Acute myeloid leukemia remains a daunting challenge to clinicians. The desire to achieve the maximum benefit of chemotherapy but also improve patient outcomes is investigated. ROS generated through several pathways promotes leukemogenesis, drug resistance, and disease relapse. Chemotherapy, the mainstay of treatment, further upregulates ROS levels. Therefore, the addition of an antioxidant to leukemia medical therapy alleviates toxicity and improves patient outcomes.

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“…[ 22 ] Leukemia, a life-threatening disease caused by malignant clonal hematopoiesis of stem and progenitor cells, is one of the top 10 cancers affecting human beings. [ 9 ] It is characterized by the accumulation of immature clonal hematopoietic cells in the bone marrow and other hematopoietic tissues, thus inhibiting normal hematopoietic function and infiltrating other tissues through enhanced self-renewal, resulting in uncontrolled proliferation, impaired differentiation, and cell apoptosis. According to the degree of differentiation, the natural course of the disease and the cells involved, leukemia can be divided into ALL, AML, CML, chronic lymphoblastic leukemia (CLL), and rare types of leukemia.…”

Section: Traditional Treatment and Antioxidant Treatment In Different Types Of Leukemiamentioning

confidence: 99%

Oxidative stress in leukemia and antioxidant treatment

Dong

Zhang

2021

Chinese Medical Journal

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Oxidative stress is caused by the imbalance between the generation of free radicals/reactive oxygen species (ROS) and the antioxidant defense systems, which can activate various transcription factors and affect their transcriptional pathways. Oxidative stress plays an important role in the occurrence and development of leukemia and is closely related to the treatment and prognosis of leukemia. The standard chemotherapy strategies for the pre-treatment of leukemia have many drawbacks. Hence, the usage of antioxidants and oxidants in the treatment of leukemia is being explored and has been preliminarily applied. This article reviews the research progress of oxidative stress and leukemia. In addition, the application of antioxidants treatment in leukemia has been summarized.

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Overview of thioredoxin system and targeted therapies for acute leukemia

Cited by 29 publications

References 76 publications

Clinical efficacy and safety of 6-thioguanine in the treatment of childhood acute lymphoblastic leukemia

Clinical efficacy and safety of 6-thioguanine in the treatment of childhood acute lymphoblastic leukemia

The significant role of redox system in myeloid leukemia: from pathogenesis to therapeutic applications

Oxidative stress in leukemia and antioxidant treatment

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