Differential redox-regulation and mitochondrial dynamics in normal and leukemic hematopoietic stem cells: A potential window for leukemia therapy

Mattes, Katharina; Vellenga, Edo; Schepers, Hein

doi:10.1016/j.critrevonc.2019.102814

Cited by 42 publications

(26 citation statements)

References 191 publications

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“…P2Et acts through different molecular mechanisms as previously described, which is evidenced by its very high antioxidant capacity in contrast to Anamu SC ( Table 2 ). The decrease of intracellular ROS could then favor the selection of LSC (leukemic stem cells) ROS-low, which are more resistant to chemotherapy [ 51 ]. A recent study shows that standard chemotherapy increases ROS levels but that this is not enough to eliminate long-term LCS, which are the cause of relapse [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

Preferential Activity of Petiveria alliacea Extract on Primary Myeloid Leukemic Blast

Ballesteros-Ramírez

Aldana

Herrera

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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The need for new therapeutic approaches to improve the response in acute leukemia (AL), either by directing therapy or with new therapeutic alternatives, has been a research and clinical interest topic. We evaluated whether blasts from AL patients were sensitive ex vivo to the induction chemotherapy and whether the extracts of Petiveria alliacea (Anamu SC) and Caesalpinia spinosa (P2Et) modulated the sensitivity of leukemic cells to death. Bone marrow samples were taken from 26 patients with de novo AL and 6 in relapse, and the cytotoxicity of the extracts alone or in combination with the chemotherapeutic was evaluated by XTT. Patients were classified as good (GR) and bad responders (BR) according to the ex vivo test. 70.5% of the GR patients to the ex vivo test achieved postinduction remission to induction chemotherapy with a median overall survival of 12.50 months versus 7.23 months in the two groups. Furthermore, it was found that the ex vivo response to extracts and chemotherapeutics is heterogeneous and shows an exclusive pattern between the extracts, Anamu being the more effective in inducing cell death. The combination of extracts with chemotherapeutic agents showed synergistic or antagonistic effects in the patients’ blasts. These results show that the ex vivo evaluation of the sensitivity to induction drugs using primary blasts from patients exhibits a correlation with the response to induction chemotherapy in patients. These analyses would allow establishing a system to predict response to treatment and determine ex vivo susceptibility to new therapies under development, among which is phytotherapeutics.

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Section: Discussionmentioning

confidence: 99%

Preferential Activity of Petiveria alliacea Extract on Primary Myeloid Leukemic Blast

Ballesteros-Ramírez

Aldana

Herrera

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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“…In a normal healthy cell, ROS levels are low which signify their lower dependence on antioxidant enzymes. Numerous studies have reported the findings that inhibition of cellular antioxidant system lead to the induction of ROS-mediated cytotoxicity (autophagy) in different types of cancers [147,149,150,151,152]. Further, elevated cellular antioxidant levels are also reported to be directly involved in developing chemoresistance in malignant cells.…”

Section: Role Of Ros In Cancer Cell Killingmentioning

confidence: 99%

Role of Reactive Oxygen Species in Cancer Progression: Molecular Mechanisms and Recent Advancements

et al. 2019

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Reactive oxygen species (ROS) play a pivotal role in biological processes and continuous ROS production in normal cells is controlled by the appropriate regulation between the silver lining of low and high ROS concentration mediated effects. Interestingly, ROS also dynamically influences the tumor microenvironment and is known to initiate cancer angiogenesis, metastasis, and survival at different concentrations. At moderate concentration, ROS activates the cancer cell survival signaling cascade involving mitogen-activated protein kinase/extracellular signal-regulated protein kinases 1/2 (MAPK/ERK1/2), p38, c-Jun N-terminal kinase (JNK), and phosphoinositide-3-kinase/ protein kinase B (PI3K/Akt), which in turn activate the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), matrix metalloproteinases (MMPs), and vascular endothelial growth factor (VEGF). At high concentrations, ROS can cause cancer cell apoptosis. Hence, it critically depends upon the ROS levels, to either augment tumorigenesis or lead to apoptosis. The major issue is targeting the dual actions of ROS effectively with respect to the concentration bias, which needs to be monitored carefully to impede tumor angiogenesis and metastasis for ROS to serve as potential therapeutic targets exogenously/endogenously. Overall, additional research is required to comprehend the potential of ROS as an effective anti-tumor modality and therapeutic target for treating malignancies.

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“…S11). It has been reported that the metabolism and redox regulation are closely related to the regulation and maintenance of HSCs in adults [41][42][43] . Mitochondria, a dynamic organelle in which many metabolic processes occur, also have critical roles in maintenance of HSCs 44 .…”

Section: Discussionmentioning

confidence: 99%

Essential role of autophagy in protecting neonatal haematopoietic stem cells from oxidative stress in a p62-independent manner

Nomura

Ito

Ooshio

et al. 2021

Sci Rep

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Autophagy is a cellular degradation system contributing to homeostasis of tissue stem cells including haematopoietic stem cells (HSCs). It plays pleiotropic roles in HSC characteristics throughout life, but its stage-specific roles in HSC self-renewal are unclear. To investigate the effects of Atg5 deletion on stage-specific HSC functions, we compared the repopulating capacity of HSCs in Atg5f/f;Vavi-cre mice from postnatal day (P) 0–7 weeks of age. Interestingly, Atg5 deficiency led to no remarkable abnormality in the HSC self-renewal capacity at P0, but significant defects at P7, followed by severe defects. Induction of Atg5 deletion at P5 by tamoxifen administration to Atg5f/f;Rosa26-Cre-ERT2 mice resulted in normal haematopoiesis, including the HSC population, until around 1 year, suggesting that Atg5 in the early neonatal period was critical for haematopoiesis in adults. Mitochondrial oxidative stress was increased by Atg5 loss in neonatal HSC/progenitor cells. Although p62 had accumulated in immature bone marrow cells of Atg5f/f;Vavi-cre mice, p62 deletion did not restore defective HSC functions, indicating that Atg5-dependent haematopoietic regulation in the developmental period was independent of p62. This study proposes a critical role of autophagy in HSC protection against harsh environments in the early neonatal stage, which is essential for healthy long-term haematopoiesis.

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Differential redox-regulation and mitochondrial dynamics in normal and leukemic hematopoietic stem cells: A potential window for leukemia therapy

Cited by 42 publications

References 191 publications

Preferential Activity of Petiveria alliacea Extract on Primary Myeloid Leukemic Blast

Preferential Activity of Petiveria alliacea Extract on Primary Myeloid Leukemic Blast

Role of Reactive Oxygen Species in Cancer Progression: Molecular Mechanisms and Recent Advancements

Essential role of autophagy in protecting neonatal haematopoietic stem cells from oxidative stress in a p62-independent manner

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