Ferroptosis: Potential therapeutic targets and prognostic predictions for acute myeloid leukemia (Review)

Abstract

Ferroptosis is a relatively recently discovered type of regulated cell death that is induced by iron-dependent lipid peroxidation. The key contributing factors to ferroptosis are the loss of glutathione peroxidase 4 which is required for reversing lipid peroxidation, the buildup of redox-active iron and the oxidation of phospholipids containing polyunsaturated fatty acids. Ferroptosis has been associated with a number of diseases, including cancers such as hepatocellular carcinoma, breast cancer, acute renal damage and neurological disorders such as Alzheimer's disease and Alzheimer's disease, and there may be an association between ferroptosis and acute myeloid leukemia (AML). The present review aims to describe the primary regulatory pathways of ferroptosis, and the relationship between ferroptosis and the occurrence and development of AML. Furthermore, the present review comprehensively summarizes the latest advances in the treatment and prognosis of ferroptosis in AML.

Keywords: acute myeloid leukemia; ferroptosis; ferroptosis mechanism; iron metabolism; lipid metabolism.

Figure 1.

Mechanisms of ferroptosis encompass a number of pathways, including those related to GSH/GPX4, iron metabolism and lipid metabolism. The GSH/GPX4 pathway includes system Xc and the MVA pathways and part of the p53 pathway. Iron metabolism is the second group, which involves other regulatory mechanisms in part of the Nrf2, NCOA4, IREB2, HSPB1 and the p53 partial pathway. The lipid metabolism route is the third group, involving factors such as p53-SAT1-ALOX15, ACSL4 and LPCAT3. AMPK signaling represents the fourth class of regulatory mechanisms involved in ferroptosis (A single arrow means promotion of the process and a red T arrow means inhibition of the pathway. Different colors represent different metabolic processes). GSH, glutathione; GPX4, glutathione peroxidase 4; GSSG, oxidized glutathione; SLC7A11, solute carrier family 7 member 11; SLC3A2, solute carrier family 3 member 2; R-OOH, lipid hydrogen peroxide; R-OH, lipid alcohols; MVA pathway, mevalonate pathway; HMG-CoA, hydroxymethylglutaryl-CoA; IPP, isopentenyl pyrophosphate; TRSP, selenocysteine-specific transfer RNA; FSP1, ferroptosis suppressor protein 1; GLS2, glutaminase 2; SAT1, spermine N1-acetyltransferase 1; LOX, lipoxygenase; ALOX15, arachidonate-15-lipoxygenase; BECN1, beclin 1; DPP4, dipeptidyl peptidase-4; Keap1, ECH associated protein 1; Nrf2, nuclear factor erythroid 2-related factor 2; HSPB1, heat shock protein family B (small) member 1; TfR1, transferrin receptor 1; STEAP3, six-transmembrane epithelial antigen of prostate 3; STEAP family member 3; DMT1, divalent metal transporter 1; ZIP8/4, zinc transporter ZIP8/4; NCOA4, nuclear receptor coactivator 4; ATG5/7, autophagy protein 5; HO-1, heme oxygenase 1; SLC25A28, solute carrier family 25 member 28; AMPK, AMP-activated protein kinase; AA, arachidonic acid; AdA, AdA, adrenoyl derivatives; PE-AA/AdA, phosphatidylethanolamines; Acetyl-CoA, acetyl coenzyme A; LPCAT3, lysophospholipid acyltransferase.