scholarly journals The Role of Reactive Oxygen Species in Acute Myeloid Leukaemia

2019 ◽  
Vol 20 (23) ◽  
pp. 6003 ◽  
Author(s):  
Sillar ◽  
Germon ◽  
DeIuliis ◽  
Dun
Keyword(s):  
Reactive Oxygen Species ◽  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Reactive Oxygen ◽  
Clinical Work ◽  
Oxygen Species ◽  
Poor Overall Survival ◽  
Wide Range ◽  
Acute Myeloid

Acute myeloid leukaemia (AML) is an aggressive haematological malignancy with a poor overall survival. Reactive oxygen species (ROS) have been shown to be elevated in a wide range of cancers including AML. Whilst previously thought to be mere by-products of cellular metabolism, it is now clear that ROS modulate the function of signalling proteins through oxidation of critical cysteine residues. In this way, ROS have been shown to regulate normal haematopoiesis as well as promote leukaemogenesis in AML. In addition, ROS promote genomic instability by damaging DNA, which promotes chemotherapy resistance. The source of ROS in AML appears to be derived from members of the “NOX family” of NADPH oxidases. Most studies link NOX-derived ROS to activating mutations in the Fms-like tyrosine kinase 3 (FLT3) and Ras-related C3 botulinum toxin substrate (Ras). Targeting ROS through either ROS induction or ROS inhibition provides a novel therapeutic target in AML. In this review, we summarise the role of ROS in normal haematopoiesis and in AML. We also explore the current treatments that modulate ROS levels in AML and discuss emerging drug targets based on pre-clinical work.

scholarly journals Critical Role of Lama4 for Hematopoiesis Regeneration and Acute Myeloid Leukemia Progression

Blood ◽  
2021 ◽  
Author(s):  
Huan Cai ◽  
Makoto Kondo ◽  
Lakshmi Sandhow ◽  
Pingnan Xiao ◽  
Anne-Sofie Johansson ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Proliferation ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Critical Role ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Bm Niche ◽  
Acute Myeloid

Impairement of normal hmatopoiesis and leukemia progression are two well-linked processes during leukemia development and controlled by the bone marrow (BM) niche. Extracellular matrix proteins including laminin are important BM niche components. However, their role in hematopoiesis regeneration and leukemia is unknown. Laminin α4 (Lama4), a major receptor-binding chain of several laminins, is altered in BM niches in mice with acute myeloid leukemia (AML). So far, the impact of Lama4 on leukemia progression remains unknown. We here report that Lama4 deletion in mice resulted in impaired hematopoiesis regeneration following irradiation-induced stress, which is accompanied with altered BM niche composition and inflammation. Importantly, in a transplantation-induced MLL-AF9 AML mouse model, we demonstrate accelerated AML progression and relapse in Lama4-/-mice. Upon AML exposure, Lama4-/- mesenchymal stem cells (MSCs) exhibited dramatic molecular alterations including upregulation of inflammatory cytokines that favor AML growth. Lama4-/- MSCs displayed increased anti-oxidant activities and promoted AML stem cell proliferation and chemoresistance to cytarabine, which was accompanied by increased mitochondrial transfer from the MSCs to AML cells and reduced reactive oxygen species in AML cells in vitro. Similarly, we detected lower levels of reactive oxygen species in AML cells from Lama4-/- mice post-cytarabine treatment. Notably, LAMA4 inhibition or knockdown in human MSCs promoted human AML cell proliferation and chemoprotection. Together, our study for the first time demonstrates a critical role of Lama4 in impeding AML progression and chemoresistance. Targeting Lama4 signaling pathways may offer potential new therapeutic options for AML.

scholarly journals The Role of Reactive Oxygen Species in Arsenic Toxicity

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 240 ◽  
Author(s):  
Yuxin Hu ◽  
Jin Li ◽  
Bin Lou ◽  
Ruirui Wu ◽  
Gang Wang ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Arsenic Exposure ◽  
Treatment Strategies ◽  
Reactive Oxygen ◽  
Cell Behavior ◽  
Arsenic Toxicity ◽  
Oxygen Species ◽  
Wide Range ◽  
Global Health Problem

Arsenic poisoning is a global health problem. Chronic exposure to arsenic has been associated with the development of a wide range of diseases and health problems in humans. Arsenic exposure induces the generation of intracellular reactive oxygen species (ROS), which mediate multiple changes to cell behavior by altering signaling pathways and epigenetic modifications, or cause direct oxidative damage to molecules. Antioxidants with the potential to reduce ROS levels have been shown to ameliorate arsenic-induced lesions. However, emerging evidence suggests that constructive activation of antioxidative pathways and decreased ROS levels contribute to chronic arsenic toxicity in some cases. This review details the pathways involved in arsenic-induced redox imbalance, as well as current studies on prophylaxis and treatment strategies using antioxidants.

scholarly journals Crosstalk between AML and stromal cells triggers acetate secretion through the metabolic rewiring of stromal cells

2021 ◽  
Author(s):  
Nuria Vilaplana-Lopera ◽  
Ruba Almaghrabi ◽  
Grigorios Papatzikas ◽  
Elena González ◽  
Alan Cunningham ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Adjuvant Therapy ◽  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Transcriptome Analysis ◽  
Stromal Cells ◽  
Oxygen Species ◽  
Nmr Studies ◽  
Metabolic Interactions ◽  
Acute Myeloid

SummaryAcute myeloid leukaemia (AML) cells interact and modulate components of their surrounding microenvironment into their own benefit. Stromal cells have been shown to support AML survival and progression through various mechanisms. Nonetheless, it is unclear whether AML cells could establish beneficial metabolic interactions with stromal cells. Here, we identify a novel metabolic crosstalk between AML and stromal cells where AML cells prompt stromal cells to secrete acetate for their own consumption. By performing transcriptome analysis and tracer-based NMR studies, we show that stromal cells present a higher rate of glycolysis, and that the secreted acetate derives from pyruvate via a reactive oxygen species (ROS)-mediated process. Our data also reveals that AML cells transfer ROS to stromal cells using gap junctions. Overall, we present a unique metabolic communication between AML and stromal cells that could be exploited as adjuvant therapy.

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