Oxidative stress in leukemia and antioxidant treatment

Dong, Chao; Zhang, Naijin; Zhang, Lijun

doi:10.1097/cm9.0000000000001628

Cited by 18 publications

(9 citation statements)

References 72 publications

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“…Hypoxia is common in many chronic tumor diseases. [ 13 ] Recent studies revealed that physiological hypoxia in BM promotes communication deficiency between hematopoietic stem cells (HSCs) and BMSCs in some hematological malignancies. [ 14 ] HIF-1α is a key transcription factor associated with hypoxia.…”

Section: Resultsmentioning

confidence: 99%

Connexin 43-modified bone marrow stromal cells reverse the imatinib resistance of K562 cells via Ca2+-dependent gap junction intercellular communication

Xiao

Wang

et al. 2023

Chinese Medical Journal

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Background:Imatinib mesylate (IM) resistance is an emerging problem for chronic myeloid leukemia (CML). Previous studies found that connexin 43 (Cx43) deficiency in the hematopoietic microenvironment (HM) protects minimal residual disease (MRD), but the mechanism remains unknown.Methods:Immunohistochemistry assays were employed to compare the expression of Cx43 and hypoxia-inducible factor 1α (HIF-1α) in bone marrow (BM) biopsies of CML patients and healthy donors. A coculture system of K562 cells and several Cx43-modified bone marrow stromal cells (BMSCs) was established under IM treatment. Proliferation, cell cycle, apoptosis, and other indicators of K562 cells in different groups were detected to investigate the function and possible mechanism of Cx43. We assessed the Ca2+-related pathway by Western blotting. Tumor-bearing models were also established to validate the causal role of Cx43 in reversing IM resistance.Results:Low levels of Cx43 in BMs were observed in CML patients, and Cx43 expression was negatively correlated with HIF-1α. We also observed that K562 cells cocultured with BMSCs transfected with adenovirus-short hairpin RNA of Cx43 (BMSCs-shCx43) had a lower apoptosis rate and that their cell cycle was blocked in G0/G1 phase, while the result was the opposite in the Cx43-overexpression setting. Cx43 mediates gap junction intercellular communication (GJIC) through direct contact, and Ca2+ is the key factor mediating the downstream apoptotic pathway. In animal experiments, mice bearing K562, and BMSCs-Cx43 had the smallest tumor volume and spleen, which was consistent with the in vitro experiments.Conclusions:Cx43 deficiency exists in CML patients, promoting the generation of MRD and inducing drug resistance. Enhancing Cx43 expression and GJIC function in the HM may be a novel strategy to reverse drug resistance and promote IM efficacy.

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Section: Resultsmentioning

confidence: 99%

Connexin 43-modified bone marrow stromal cells reverse the imatinib resistance of K562 cells via Ca2+-dependent gap junction intercellular communication

Xiao

Wang

et al. 2023

Chinese Medical Journal

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“…Compared to single trace elements, the positive value of SCZR was meaningful, and the ratio suggests that patients were in a condition of oxidative stress [27]. While oxidative stress plays an important role in the occurrence and development of leukaemia and is closely related to the treatment and prognosis of leukaemia [38]. Meanwhile, the SCZR was an indicator of the nutritional status of Zn [39].…”

Section: Discussionmentioning

confidence: 99%

The trace that is valuable: serum copper and copper to zinc ratio for survival prediction in younger patients with newly diagnosed acute myeloid leukaemia

Shi

Wei

et al. 2023

BMC Cancer

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Purpose No data on predicting the survival of AML patients based on the level of trace elements in the serum have been presented to date. The aims of this prospective cohort study were as follows: (i) to evaluate the serum Cu and Zn levels in people from Northeast China, (ii) to assess the association between the serum Cu level (SCL) and Cu to Zn ratio (SCZR) and clinical and nutrition data, and (iii) to investigate the predictive values of the SCL and SCZR in newly diagnosed de novo AML patients. Methods A total of 105 newly diagnosed AML patients and 82 healthy controls were recruited. The serum Cu and Zn levels were determined by inductively coupled plasma spectrometry. The associations of SCL and SCZR with the survival of these AML patients were assessed by Cox proportional hazards models. Results Both SCL and SCZR were positively related to the blast percentage of bone marrow and C-reactive protein, negatively related to albumin level and CEBPA double mutation and were significantly associated with worse overall survival and disease-free survival. Meanwhile, patients with higher SCL had worse CTCAE levels, and patients with higher SCZR showed less complete remission during the first course of induction chemotherapy. Moreover, higher SCZR was positively associated with ELN risk stratification, and was negatively associated with haemoglobin level and prognostic nutritional index (PNI). Conclusion The SCL and SCZR are associated with long-term survival in patients with newly diagnosed AML undergoing intensive induction and may serve as important predictive biomarkers.

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“…The imbalance between the production of reactive oxygen species (ROS) and antioxidant defense mechanisms, which can activate different transcription factors and alter their transcriptional pathways, results in oxidative stress. Leukemia's occurrence and progression, as well as its treatment and prognosis, are all directly impacted by oxidative stress (Dong et al, 2021).…”

Section: Oxidative Stressmentioning

confidence: 99%

Pre-leukemic Cell Detection and Leukemic Transformation of a Normal Marrow Cell: A Mini review

Chhetri

Thapa

Shrestha

et al. 2022

Int J Appl Sci Biotechnol

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The hematopoietic cells are multipotent primitive cells, which differentiate into either common myeloid and lymphoid progenitor. However, if there an abnormality in this process of differentiation, condition of leukemia arises, which is the 11th leading cause of cancer-related mortality worldwide in the year 2018. These abnormalities are brought about by array of mutations occurring at cellular level. According to the two-hit model hypothesis, key oncogenic events are classified into two classes: class I mutations and class II mutations. Class I mutations are those that causes activation of the receptor tyrosine kinase (RTK), FLT3, c-kit (KIT), and Ras signaling pathways thereby increasing proliferation rate of progenitor cells. Class II mutations include recurrent chromosomal abnormalities such as t(8; 21), inv(16), and t(15; 17), which result in fusion transcripts of RUNX1/ETO, CBF/MYH11, and PML/RAR, respectively that eventually impair hematopoietic differentiation. The factors associated with leukemia can be biological, chemical or socio-economical. The advancement in the researches on the topic have aided to the development of various technologies such as detection of DNMT3A and xenografts assays, in order to detect these mutations in pre-leukemic cells. This review aims to provide an introduction to the condition, its types and provide brief summary on genes and mutations responsible for the condition. The factors associated with leukemia and technologies involved in the detection of leukemia are also reviewed.

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Oxidative stress in leukemia and antioxidant treatment

Cited by 18 publications

References 72 publications

Connexin 43-modified bone marrow stromal cells reverse the imatinib resistance of K562 cells via Ca2+-dependent gap junction intercellular communication

Connexin 43-modified bone marrow stromal cells reverse the imatinib resistance of K562 cells via Ca2+-dependent gap junction intercellular communication

The trace that is valuable: serum copper and copper to zinc ratio for survival prediction in younger patients with newly diagnosed acute myeloid leukaemia

Pre-leukemic Cell Detection and Leukemic Transformation of a Normal Marrow Cell: A Mini review

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