Ferroptosis in Acute Leukemia

Abstract

Ferroptosis is an iron-dependent cell death pathway that is different from apoptosis, pyroptosis, and necrosis. The main characteristics of ferroptosis are the Fenton reaction mediated by intracellular free divalent iron ions, lipid peroxidation of cell membrane lipids, and inhibition of the anti-lipid peroxidation activity of intracellular glutathione peroxidase 4 (GPX4). Recent studies have shown that ferroptosis can be involved in the pathological processes of many disorders, such as ischemiareperfusion injury, nervous system diseases, and blood diseases. However, the specific mechanisms by which ferroptosis participates in the occurrence and development of acute leukemia still need to be more fully and deeply studied. This article reviews the characteristics of ferroptosis and the regulatory mechanisms promoting or inhibiting ferroptosis. More importantly, it further discusses the role of ferroptosis in acute leukemia and predicts a change in treatment strategy brought about by increased knowledge of the role of ferroptosis in acute leukemia.

Synergistic interactions of cytarabine-adavosertib in leukemic cell lines proliferation and metabolomic endpoints

“…Although decreased Krebs cycle and electron transport activity (two of the main enriched processes in Fig. 6C ) may contribute to the metabolic reprogramming and mitochondrial respiratory injury as part of the Warbug effect [ 59 - 62 ] these can also lead to apoptosis, ferroptosis and cell death, adding another dimension to the combinatorial synergistic action of cytarabine-adavosertib [ 63 , 64 ]. In addition, decreased Krebs cycle activity can also lead to decreased accummulation of lactate via diminished conversion of oxaloacetate→phosphoenolpyruvate→pyruvate→lactate counteracting lactic acidosis and the lactate stimulation of cancer cell proliferation and suppression of anti-tumor immunity other hallmarks of the Warburg effect [ 59 - 62 ].…”

Ferroptosis in chronic obstructive pulmonary disease: From cellular mechanisms to therapeutic applications

“…Recently, ferroptosis, a form of cell death driven by iron-dependent lipid peroxidation, has been associated with the pathogenesis of COPD. [ 1 ] Multiple signaling pathways, such as glutathione peroxidase 4 (GPX4), ferroptosis suppressor protein 1 (FSP1), and tetrahydrobiopterin-dependent pathways, as well as iron metabolism, are involved in regulating ferroptosis [ 2 , 3 ] [Figure 1 A]. Here, we provide a comprehensive overview of recent advances in understanding the role of ferroptosis in COPD, highlighting potential therapeutic strategies targeting ferroptosis for treating the disease.…”