Ferroptosis: Potential therapeutic targets and prognostic predictions for acute myeloid leukemia (Review)
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- Published online on: September 30, 2024 https://doi.org/10.3892/ol.2024.14707
- Article Number: 574
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Copyright : © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].
Abstract
Introduction
AML is a malignant clonal proliferative disease of hematopoietic stem cells. The diagnosis and therapy of AML have advanced in recent years due to continuous research and an improved understanding of the etiology of the disease (1). Numerous targeted small-molecule inhibitors have been approved for the treatment of AML, which have demonstrated favorable curative results, including chemotherapy and hematopoietic stem cell transplantation (2). AML has a poor prognosis and a high rate of recurrence (1,2). Thus, further research to explore novel therapeutic drugs to improve the prognosis of AML is required. The diagnosis of AML is primarily dependent on clinical presentation and pathological features, particularly the presence of specific gene mutations, such as RUNX1 and TP53, which are often associated with poor prognosis. In addition, according to World Health Organization (WHO) standards, the diagnosis of AML requires that the proportion of primitive cells (blastocytes) in the bone marrow or peripheral blood be at or above 20%. Comprehensive analysis of these factors is essential for accurate diagnosis and effective treatment planning (3).
With an increasing understanding of iron metabolism and the identification of ferroptosis as a novel type of regulated cell death dependent on iron, novel therapeutic options have emerged in recent years (4,5). The ability to induce effective tumor cell death, while protecting healthy cells is critical for cancer therapy. For tumor survival and growth, cancerous cells require larger quantities of iron than healthy cells (6). Given their dependency on iron, tumor cells are more vulnerable to iron-induced apoptosis (7,8). Regulation of the ferroptotic pathway to prevent the development and growth of malignancies has garnered increasing interest in recent years (9–11). The present review aims to provide an overview of ferroptosis in the incidence, development, prognosis and as a potential therapeutic target of AML.
Mechanisms of ferroptosis
Ferroptosis, a unique type of cell death characterized by the buildup of lipid reactive oxygen species (ROS) and iron dependency, was initially described by Dixon et al (12) in 2012. Ferroptosis describes a mode of cell death distinct from apoptosis, necrosis and autophagy. Ferroptosis is characterized by reduced mitochondrial volume, increased lipid bilayer density, and diminished or absent mitochondrial cristae, while the cell membrane and the nuclear morphology remain unaffected (13,14). In biological terms, lipid peroxide metabolism is catalyzed by reduced glutathione peroxidase 4 (GPX4) activity and intracellular glutathione (GSH) levels (15). Ferroptosis is induced by the Fenton reaction, in which Fe2+ oxidizes lipids and generates significant quantities of ROS (16,17).
Ferroptosis mechanisms can be broadly classified into four categories: i) The GSH/GPX4 pathway, ii) the inhibitory system Xc, iii) the mevalonate (MVA) pathway; and iv) p53 regulation (Fig. 1) (13). The solute carrier family 7 member 11 (SLC7A11) and SLC3A2 subunits constitute the amino acid anti-transporter system Xc, which is present in the cell membranes of various cell types (18,19). Glutamate and cystine are imported and exported by system Xc in a 1:1 ratio. The cystine that is imported into the cell is reduced to form GSH. In the presence of GPX, GSH can reduce ROS. GPX4 is a crucial regulator of iron-induced mortality in the GPX family (20). GPX4 converts lipid hydrogen peroxide (R-OOH) to lipid alcohols (R-OH), which limits iron-dependent lipid ROS generation and protects membrane integrity from damage induced by ROS buildup (21). The MVA pathway synthesizes isoprene units such as isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP) from acetyl coenzyme A (acetyl-CoA) (22). This pathway also contributes to stabilization of the transport RNA (tRNA) needed for selenocysteine incorporation into selenoproteins, through protein isoprenylation. A key selenoprotein affected is GPX4, which clears toxic lipid peroxides to suppress oxidative cell damage. Inhibition of the MVA pathway, by statins for example, reduces IPP/DMAPP production and selenoprotein synthesis, which reduces GPX4 activity (23,24). This impairs the elimination of lipid peroxides and sensitizes cells to ferroptosis. However, an impaired mevalonate pathway also reduces the synthesis of coenzyme Q10, an antioxidant that partners with ferroptosis suppressor protein 1 (FSP1) and NADH to neutralize the toxic lipid radicals that accumulate in cells. Thus, the coenzyme Q10-FSP1-NADH system acts in an anti-ferroptotic manner, downstream of mevalonate pathway inhibition to delay the induction of iron-mediated oxidative cell death (25).
Ferroptosis is regulated by p53 via two mechanisms (26,27). Ferroptosis has been reported to be inhibited by p53 in colorectal cancer cells through the formation of a dipeptidyl peptidase-4 (DPP4)-p53 complex and the subsequent translocation of the DPP4 enzyme from the cell membrane to the nucleus. This process reduces the activity of DPP4 on the cell membrane, thereby decreasing lipid peroxidation and ultimately inhibiting ferroptosis (28). p53-mediated inhibition of ferroptosis also increases SLC7A11 expression levels through the inhibition of Nrf2-mediated gene expression, which leads to increased GSH synthesis and lipid peroxide clearance (29,30). p53 can also contribute to ferroptosis through several approaches: i) The suppression of system Xc, which reduces cystine uptake and GSH production (28); and ii) transcriptional activation of glutaminase-2 to decrease GSH levels and GPX4 activity (27). The latter mechanism is related to iron metabolism, such as via the p62-kelch like ECH associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) regulatory pathway, nuclear receptor coactivator 4 (NCOA4) pathway that is related to ferritin metabolism, iron responsive element binding protein 2 (IREB2), p53 and heat shock protein family B (small) member 1 (HSPB) regulatory pathways (13). Intracellular iron levels are crucial in order to maintain intracellular homeostasis and increased iron levels can induce a Fenton reaction, which results in the formation of intracellular ROS. Lipid peroxidation processes can be induced by excess levels of ROS and lead to ferroptosis (31). The transferrin receptor 1 (TfR1) is a membrane protein that binds to the Fe3+/transferrin complex, which allows iron to be released into endocytic vesicles inside the cell (9). Once inside the vesicles, Fe3+ is reduced to Fe2+ by the iron reductase enzyme, STEAP. Fe2+ then enters the cytosol, creating an unstable pool of free iron known as the labile iron pool (LIP) (32). The LIP is regulated by either the zinc-iron regulatory proteins ZIP8 and ZIP14, or the divalent metal transport protein 1 (33). The iron from the LIP can be stored inside the protein ferritin or transferred back out of the cell via the iron export protein ferroportin (FPN) to keep the LIP levels low and prevent iron-induced cell death. Through the utilization of TfR1 and FPN, cells can control iron import and export to meet its needs while avoiding excess free iron that could cause oxidative damage (34). In 2016, Sun et al (35) demonstrated that the p62-Keap1-Nrf2 pathway controls the suppression of ferroptosis in hepatocellular carcinoma. The antioxidant response is notably regulated by Nrf2, which can reduce ferroptosis and improve tumor chemotherapy response and radiation resistance (36). Keap1 targets Nrf2 for ubiquitination and degradation, thus inhibiting Nrf2 (37,38). p62 is a multifunctional autophagy receptor, and the accumulation of p62 reduces the inhibition of Keap1 and promote the release of Nrf2 (39).
Within the NCOA4 pathway, a process known as ferritin phagocytosis, which is mediated by the cargo receptor NCOA4, can cause a subsequent release of iron into the cytoplasm to reduce iron toxicity (40). Ferritin is made up of the ferritin heavy chain 1 (FTH1) and the ferritin light chain (FTL) (41). Erastin-induced ferroptosis was inhibited by increasing the expression levels of FTL and FTH1 while significantly decreasing the expression levels of IREB2, a crucial transcription factor of iron metabolism (42,43). Heat shock protein family B (small) member 1 (HSPB1) overexpression can further raise intracellular iron content by increasing TRF1 expression and preventing ferroptosis (44). Previous studies have uncovered additional mechanisms by which p53 regulates ferroptosis by modulating iron metabolism and availability (45). p53 promotes ferroptosis by transcriptionally activating TfR1 and the mitochondrial iron importer solute carrier family 25 member 28 (SLC25A28), which results in increased uptake and accumulation of reactive iron, that sensitizes cells to oxidative damage (46). In addition, p53 can drive the degradation of the iron-storage protein ferritin by activating NCOA4. This results in the release of stored iron to further increase reactive intracellular iron levels (47). Conversely, p53 can also increase the expression of heme oxygenase-1 (HO-1) which reduces overall cellular iron levels. By decreasing iron availability, HO-1 activity inhibits lipid peroxidation and suppresses ferroptosis sensitivity (48).
The third mechanism is related to lipid metabolism pathways, such as the p53-SAT1-arachidonic acid lipoxygenase 15 (ALOX15), ACSL4 and lysophospholipid acyltransferase (LPCAT3) pathways (9). The process of lipid peroxidation is crucial to ferroptosis. Spermine N1-acetyltransferase 1 (SAT1) is the transcriptional target of p53 in the p53-SAT1-ALOX15 pathway, and activation of SAT1 can induce lipid peroxidation to encourage ferroptosis, which is tightly connected through ALOX15 control (13). Lipid peroxidation is initiated by the formation of arachidonic acid (AA)/adrenoyl derivatives (AdA). Polyunsaturated fatty acids (PUFAs) such as AA and AdA are esterified to form PUFA-PL complexes (PE-AA/AdA) under the action of ACSL4 and LPCAT, resulting in the accumulation of PE-AA/AdA in the cell membrane to produce lipid peroxides via LOX activity and Fenton reactions, which induce ferroptosis (49). The enzymatic pathway utilizes LOXs, which are non-heme iron-containing dioxygenases. PE-AA/AdA serve as substrates for 15-LOX to form phospholipid hydroperoxides (PE-AA/AdA-OOH) (36,40). These peroxyl radicals propagate further peroxidation of neighboring PUFAs (32). In addition, in the non-enzymatic pathway, free redox-active iron reacts with PE-AA/AdA via Fenton reactions to generate membrane-destabilizing lipid peroxides (50). In both pathways, the iron-dependent peroxidation of membrane PUFAs catalyzed by PE-AA/AdA intermediates results in excessive free radical damage, depletion of antioxidants, loss of membrane integrity and ultimately, execution of regulated ferroptotic cell death (9,51).
Finally, there are other regulatory pathways involved in ferroptosis, such as the AMP-activated protein kinase (AMPK) signaling pathway. AMPK acts as a sensor of the cellular energy status and contributes to the preservation of energy homeostasis (52). To prevent PUFA biosynthesis and ferroptosis, AMPK can mediate the phosphorylation of acetyl-CoA carboxylase. However, AMPK also inhibits SLC7A11-mediated cystine transport and increases ferroptosis by modulating the phosphorylation of beclin1 (BECN1) (15,53).
Role of ferroptosis in the development and progression of AML
AML is a heterogeneous disease characterized by constitutively activated oncogenic signals, high mortality rates and a poor prognosis. It is typically treated with chemotherapy and patient survival rates are poor (54). Therefore, novel therapeutic approaches are required to improve the management of the disease (55). Iron serves a role in hematopoiesis and is a necessary component of human cells. After interacting with the transferrin-iron complex, the membrane protein TfR1 releases iron via endocytosis. When TfR1 expression is suppressed, iron deprivation reduces the ability of hematopoietic stem cells to regenerate and affects the proliferation and differentiation of hematopoietic progenitor cells. ROS accumulation, induced by excessive iron, can result in oxidative stress which can damage proteins, DNA, lipids and even induce cell death (14,53). Patients with AML frequently exhibit severe symptoms resulting from iron overload, primarily due to the extensive blood transfusions required to manage anemia caused by abnormal erythropoiesis and chemotherapy. These symptoms include heart failure, liver fibrosis, diabetes, endocrine disorders, fatigue, and weakness, significantly impacting the patients' quality of life and prognosis (40). Additionally, the rapid proliferation of specific hematopoietic precursor cells in patients with AML leads to an increased demand for iron (56). Thus, given the tendency for iron-overload and the iron dependency of AML, the induction of ferroptosis represents a promising therapeutic approach (40,56).
GPX4 is an antioxidant enzyme that uses GSH to transform toxic lipid peroxides into non-toxic lipols, thereby protecting cells from ferroptosis. Previous studies (49,57) have demonstrated that GPX4 is upregulated in AML cells, which enables cells to restrict ferroptosis through reduced lipid peroxide levels, which ultimately increases AML cell survival and drug resistance (58). Consequently, GPX4 serves a critical role in AML progression and represents a promising therapeutic target. The survival pathway of cancer cells, particularly the antioxidant response regulated by Nrf2, serves a crucial role in the defense against apoptosis, which is a key factor in cancer cell survival (59). Nrf2 has been linked to the development of AML and previous studies suggest that it can be regulated by NF-κB in AML. This activation of the Nrf2-dependent antioxidant defense response provides growth advantages and resistance to treatment for AML cells (60).
Lipid metabolism and ferroptosis are intricately intertwined, as the emergence of lipid peroxides is one of the hallmarks of ferroptosis (61). In patients with AML, lipid homeostasis is disrupted, and PUFAs and other unsaturated fatty acids present in AML cells contribute to the onset and progression of the disease (62). Although there is limited research on the mechanisms underlying the development of AML, it is clear that further investigation is necessary to elucidate the specific molecular mechanisms involved (Table I).
Ferroptosis in AML therapy
AML is the most common type of leukemia in adults and is typically treated with chemotherapy. However, chemotherapy can have severe side effects and cause drug resistance in leukemia cells (63). Although hematopoietic stem cell transplantation can cure AML in a number of cases, its widespread use is limited. For instance, the relapse rate post-transplant is relatively high, particularly among high-risk patients. In addition, patients face significant infection risks during and after the transplantation process. Therefore, there is an urgent need for more effective and accessible treatment for AML. Recent studies have shown that inducers of ferroptosis, a process that involves the buildup of reactive oxygen species (ROS) and lipid peroxidation, have potential to treat certain types of cancer (64,65).
Numerous substances, including eprenetapopt (APR-246), aldehyde dehydrogenase 3 family member A2 (ALDH3A2), poly(lactic acid)-glycolic acid-encapsulated glycyrrhetinic acids (GCMNPs), glutathione-bioimprinted nanoparticles targeting of N6-methyladenosine FTO demethylase (GNPIPP12MA), gold nanorods (GnR) functionalized with chitosan and a 12-mer peptide 12 (GnRA-CSP12) and GCFN, have been found to induce ferroptosis in AML cells by disrupting the balance between GSH and ROS and inhibiting GPX4 synthesis (51,66–69). In a study by Birsen et al (66), APR-246 was reported to induce ferroptosis in AML cells by decreasing GSH concentration and increasing ROS and lipid peroxides. This treatment may be effective for different subtypes of patients with AML, as it works regardless of the presence of p53 mutations. It was also reported that ferroptosis inducers, RAS-selective lethal (RSL3) and FINO2, a 1,2-dioxolane, increased the antileukemic activity of APR-246 in AML in vitro (70,71). In phase II studies of myelodysplastic syndromes/AML with APR-246, adverse neurological events were reported in over one-third of patients who received APR-246 (72). Additionally, previous research has demonstrated an association between ferroptosis and neurological disorders, particularly neurodegenerative disorders (73). ALDH3A2 is an aldehyde dehydrogenase that is present in both healthy myeloid cells and primary AML cells (67). It is essential for the detoxification of aliphatic aldehydes and the synthesis of 16- and 18-carbon fatty acids. Yusuf et al (67) reported that AML cells that were deficient in ALDH3A2 had altered biosynthetic pathways, exhibited increased oxidative damage and had an altered cellular lipid composition. It was reported that lipid peroxidation was associated with the induction of ferric death and an increase in lysophospholipids was observed experimentally, particularly in the absence of polyunsaturated fatty acid tails as a marker of ferroptosis. Moreover, ALDH3A2 depletion caused ferroptosis in leukemia cells and acted synergistically with GPX4 inhibition. Furthermore, ALDH3A2 depletion caused iron depletion in leukemia cells and preserved normal hematopoietic function. Hence, the inhibition of ALDH3A2 in combination with ferroptosis inducer drugs, particularly GPX4 inhibitors, may be a potential treatment for AML (67).
CircKDM4C is a cyclic RNA produced by the KDM4C gene. According to Dong et al (74), circKDM4C increases p53 expression levels by regulating the microRNA (miRNA) hsa-let-7b-5p. Specifically, circKDM4C acts as a sponge for hsa-let-7b-5p, reducing its inhibitory effect on p53, thereby enhancing p53 expression levels. The increase in p53 expression levels lead to an increase in intracellular iron concentration and ROS expression levels and caused ferroptosis in AML cells. Initially identified as a regulator of cell proliferation in Caenorhabditis elegans, miRNA hsa-let-7 was found to be upregulated in AML. Previous research has demonstrated that p53 can block the cystine system by downregulating SLC7A11, which in turn decreases GPX4 activity. This decrease in GPX4 activity led to a decrease in the antioxidant capacity of leukemia cells and an accumulation of ROS, causing ferroptosis (75). As a result, circKDM4C presents a potential target for the treatment of patients with AML.
Yu et al (76) developed a ferroptosis-inducing nanotherapeutic drug (GCFN) based on glutathione reactive cysteine polymer. To evaluate the efficacy of GCFN in treating AML, a mouse model of aggressive AML was developed. GCFN could effectively induce lipid peroxidation and ferroptosis in AML cells by reducing the expression levels of intracellular GSH and inhibiting the activity of GPX4, thus providing a basis for GCFN as a potential treatment for AML.
Immunotherapy is a valuable therapeutic method that has been successfully applied in clinical settings. Breaking autoantigen immune tolerance is essential for antitumor immunotherapy (51). Targeted therapies are a promising research strategy because they have been shown to enhance tumor immunity by activating T cells, modulating the tumor microenvironment, enhancing antigen presentation and inhibiting immune checkpoints, thereby improving treatment effectiveness and reducing the likelihood of recurrence (77,78). For example, studies have found that the combination of GCMNPs with PD-L1 blockers may potentially improve efficacy in the management of leukemia (68). GNPIPP12MA enhances anti-leukemia immunity by increasing cytotoxic T cell infiltration (79). GnRA-CSP12 disrupts intracellular REDOX balance, regulates epigenetic transcriptomics, and further enhances cytotoxic response of T cells. These combination therapies have shown promising results in preclinical models, showing great potential to improve the treatment of leukemia (80).
GCMNPs are highly specific to cancer cells and have low toxicity in AML (68). Through the inhibition of GPX4, GCMNPs can induce ferroptosis in AML cells, which increases lipid peroxide levels (51). In this study, a mouse model of AML was successfully used to evaluate the immune response to cancer immunotherapy, particularly against AML and colorectal cancer. Encouragingly, the animals did not experience any weight loss or damage to kidney, heart, liver or lung tissue during treatment. This result not only demonstrates the efficacy of the treatment, but also highlights its safety, providing valuable insights for future cancer immunotherapies. This demonstrates the significant value of the AML mouse model in assessing the efficacy and safety of cancer immunotherapy. Ferumoxytol and GCMNPs can also work together to increase the Fenton reaction and cause ferroptosis. Additionally, the combination of GCMNPs, Ferumoxytol and anti-PD-L1 improved T cell immune responses against leukemia (68).
In AML, fat mass and obesity-associated protein (FTO), an N6-methyladenosine (m6A) demethylase, contributes to carcinogenesis by preventing the expression of immune checkpoint genes, particularly LILRB4. Knockdown of FTO reduced the growth of leukemia stem cells and prevented leukemia cells from escaping the immune system (79). GNPIPP12MA is an FTO inhibitor-loaded GSH-bioimprinted nanocomposite (69). Through the FTO/m6A pathway, GNPIPP12MA induces GSH depletion to inactivate GPX4, inhibit the decrease in LPO, increase intracellular iron accumulation and lead to the selective ferroptosis of AML cells. GNPIPP12MA therefore has a wide range of anti-AML effects at relatively low doses. Additionally, GNPIPP12MA could improve antileukemic immunity by increased infiltration of cytotoxic T cells (69,79).
Nanoparticles of gold hexadecyltrimethylammonium bromide and sodium oleate are used as a binary surfactant combination to create GnRA-CSP12 (80), which are GnRs with various aspect ratios. GnRA-CSP12 is selectively taken up by leukemia cells through targeted endocytosis, disrupting the intracellular redox balance, inducing ferroptosis and regulating epitranscriptomics by eliminating Fe2+-dependent m6A demethylase activity. This enhances the cytotoxic response of T cells, thereby improving immunotherapy efficacy. Specifically, GnRs reduced GSH expression levels through the formation of Au-S bonds with GSH, disrupting the GSH/ROS balance and ferroptosis of leukemia cells. In the AML mouse model treated with GnRs, no changes in body weight or pathological alterations in major organs were observed and no significant toxic effects or side effects were detected.
The regulation of ferroptosis also involves a number of signaling molecules and pathways. For example, the quinazolinone derivatives, Erastin and high mobility group box 1 (HMGB1) (81), regulate ferroptosis through the JNK/p38 pathway, while dihydroartemisinin (DHA) and typhaneoside (TYP) regulate ferroptosis through the AMPK signaling pathway (82,83). 4-amino-2-trifluoromethyl-phenyl retinate (ATPR) modulates ferroptosis via Nrf2 signaling (84). Imetelstat influences ferroptosis by modulation of the ACSL4 and FADS2 molecular signaling pathways (85). Finally, Honokiol regulates ferroptosis by upregulating the expression levels of heme oxygenase 1 (HMOX1) (86).
The discovery of Erastin was initially prompted by its ability to selectively induce cell death in cancer cells with mutant RAS (87). In a study conducted by Yu et al (88), it was demonstrated that Erastin increased the susceptibility of non-acute promyelocytic leukemia (APL) AML cells to chemotherapeutic drugs cytarabine and doxorubicin in an RAS-independent manner. Erastin-induced ferroptosis activates the JNK and p38 signaling pathways, but not the ERK/MAPK pathway. Low doses of Erastin, in part due to ferroptosis, increased the susceptibility of non-APL AML cells to cytarabine and doxorubicin.
HMGB1 is a transcription factor that is crucial to the etiology and chemotherapeutic resistance of leukemia (89). Wen et al (81) demonstrated that HMGB1 is directly involved in Erastin-induced ferroptosis and is a significant regulator of the process. It was reported that the RAS-JNK/p38 pathway is utilized by HMGB1 to regulate Erastin-mediated ferroptosis and the in vivo examination of HMGB1 expression levels did not have a significant impact on experimental animals.
DHA, a natural antimalarial compound found in the Chinese herb Artemisia annua, has been reported to significantly inhibit the activity of AML cells (82,90). DHA activates AMPK phosphorylation to downregulate the activity of the mTOR/p70S6k signaling pathway, induces autophagy in AML cells, speeds up ferritin degradation, increases the size of the unstable iron pool, increases cell ROS accumulation and ultimately causes ferroptosis in AML cells.
TYP is a major flavonoid compound extracted from typha pollen. Zhu et al (83) reported that TYP serves a significant role in inhibiting the proliferation of AML cells by promoting the activation of the AMPK signal, inducing significant autophagy of AML cells and ultimately causing ferritin degradation, ROS accumulation and ferroptosis. They reportedly assessed the toxicity of TYP by observing weight changes and pathological changes in major organs such as the liver, spleen, kidney and lungs in mice during treatment. The results showed that no weight loss or pathological changes in major organs were observed in mice treated with TYP, indicating a low level of toxicity and good safety.
An all-trans retinoic acid (ATRA) derivative known as ATPR, which was designed and synthesized by Du et al (84), exhibits more potent anticancer properties compared with ATRA. ATPR-mediated induction acts through the regulation of iron homeostasis and ROS levels by inhibiting the expression of Nrf2. Nrf2 is an important antioxidant reaction factor and its inhibition results in an increase in the sensitivity of cells to oxidative stress, which promotes autophagy (91). In addition, ATPR also regulates iron homeostasis by increasing ROS levels, a mechanism that may involve the degradation of ferritin and iron metabolism-related proteins, thereby releasing bound iron and increasing LIP and ROS levels, further inducing ferroptosis (92).
Imetelstat is a small oligonucleotide inhibitor of telomerase, a ribonucleoprotein complex that protects and prolongs the telomeres at the end of chromosomes, a process that is involved in cellular senescence and cellular aging (85). Imetelstat acts as a potent inducer of ferroptosis, by promoting excessive lipid peroxidation and oxidative stress in AML, via regulation of PUFA metabolism, which is itself mediated by ACSL4 and FADS2. The preclinical efficacy of imetelstat was evaluated using an AML patient-derived xenograft model. The combination of imetelstat and standard induction chemotherapy, consisting of cytarabine and anthracycline, induced oxidative stress, causing AML cells to become sensitive to imetelstat-induced lipid peroxidation and ferroptosis, which increased the efficacy of chemotherapy on AML. This demonstrated that imetelstat could effectively reduce the burden of AML and delay the recurrence following oxidative stress-induced chemotherapy (85).
Honokiol is a bioactive bisphenol phytochemical that can be isolated from the bark, seed balls and leaves of trees belonging to the genus Magnolia (86). It has potent antioxidant, anti-inflammatory, anti-angiogenic and anticancer properties. Notably, honokiol triggers ferroptosis in AML cells by increasing the expression levels of HMOX1, and furthermore, zinc protoporphyrin, an HMOX1 inhibitor, prevented the honokiol-induced ferroptosis of several AML cell lines (THP-1, U-937 and SKM-1 cells) (86). However, the potential of honokiol as a broad-spectrum antileukemic therapy remains to be determined.
In recent years, remarkable progress has been made in the study of drugs targeting ferroptosis drugs for AML. These drugs include small molecule inhibitors, natural compounds and drugs prepared using nanotechnology, which have demonstrated potential therapeutic effects in clinical trials (Table II). Nevertheless, the value of these drugs compared with standard AML treatments still requires further evaluation. Future studies should focus on the safety, efficacy and long-term effects of these drugs in clinical use to determine their practical use in the treatment of AML, with the goal of improving the accuracy of prognostic predictions and developing personalized treatment plans. The varying sensitivities of different subgroups of patients with AML to various treatments, as well as individual differences between patients should be taken into consideration in further research. This research will be of notable significance to improve the survival rates and quality of life of patients.
Ferroptosis and the prognosis of AML
Dysregulated maturation and differentiation of hematopoietic stem cells and malignant cloning are associated with the formation and progression of AML, a heterogeneous hematological disease (93). The clinical effectiveness in patients with AML was significantly increased following the optimization of targeted treatment and hematopoietic stem cell transplantation, specifically reflected in the significant increases in complete remission rates and overall survival. However, the long-term survival of patients is still limited and patient prognosis remains poor. The association between ferroptosis-related genes (FRG) and the prognosis of AML has garnered interest, due to interest in ferroptosis as a possible therapeutic target for the management of cancer. To improve patient risk adaptation therapy, it is necessary to investigate the prognostic significance of FRGs by establishing a clinical prognostic model for predicting survival risk in patients with AML (Table III).
A previous study showed the normalized levels of each FRG and the regression coefficients were used to create the AML risk score, which was based on the sum of numerous clinical variables (94). The normalized level of each FRG and its regression coefficient were used to calculate the AML risk score. Then, based on a median risk score, patients with AML were split into low-risk and high-risk groups. According to the survival analysis, the mortality rate in the low-risk group was significantly reduced and overall survival was significantly increased. Cox regression analysis was used to develop a combined risk score using the clinical characteristics of patients with AML using data from TCGA, such as age and sex (95). The prognostic risk score model was employed as a prognostic factor independent of other clinical parameters to successfully guide prognosis prediction, based on the multivariate Cox regression analysis, but it has not yet been implemented in clinical practice (96). Another study on the prognosis of two FRGs, DNAJ heat shock protein family member B6 (DNAJB6) and HSPB1, showed they were favorably and adversely correlated with the prognosis of patients with AML, respectively, in a prognostic model created using copy number variation (CNV)-driven FRGs (96). A total of eight ferroptosis regulators PGD, ACSF2, CISD1, DPP4, GPX4ADDIN, SQLE, AIFM2 and CHAC1] were used to create a predictive model, and were all associated with poor prognosis in patients with AML (97,98). In another study, ZFPM2, ZNF560, ZSCAN4, HMX2, HRASLS, LGALS1, LHX6, CCL23 and FAM155B were high-risk genes for prognosis in patients with AML in the prognostic model created using 18 regulators of ferroptosis (99), whereas MXRA5, PCDHB12, PRINS, TMEM56, TWIST1, ASTN1, DLL3, EFNB3 and FOXL1 were genes associated with a favorable prognosis. Another prognostic risk model for AML based on 12 FRGS, including 10 high-risk genes (GPX4, CD44, CISD1, SESN2, LPCAT3, AIFM2, AKR1C2, SOCS1, ACSL5 and HSPB1) and two protective genes (ACSL6 and G3BP1) (100), showed that these genes served an important role in regulating ferroptosis and tumor development (101). In vitro research demonstrated that HIVEP3 was a factor in ferroptosis. Using a LASSO model, the integration of HIVEP3 with AIFM2 and LPCAT3 increased the precision of HIVEP3 for predicting a worse prognosis in patients with AML (102). In recent years, the function of these genes and their importance in cancer prognosis have become a focus of increased research. These studies contribute to the understanding of the molecular mechanisms of cancer and may guide future treatment strategies.
DNAJB6 acts as a molecular chaperone protein that functions with Hsp70 to ensure the correct folding of proteins (103). The naturally increased expression of DNAJB6 has been found to decrease GPX4 activity, leading to an increase in ferroptosis. In certain types of cancer, such as esophageal squamous cell carcinoma, downregulated DNAJB6 expression levels have been associated with anticancer effects. Conversely, in AML, low DNAJB6 expression levels were associated with an improved prognosis, which suggested that it may act as a protective factor (104). DNAJB6 is a member of the small heat shock protein family, and as such, HSPB1 is involved in regulating cytoskeletal organization and preventing the aggregation of abnormally folded proteins (105). In breast cancer, non-small cell lung cancer, gastric cancer, and prostate cancer, aberrant expression levels of HSPB1 have been associated with aggressive tumor behavior, chemotherapy resistance, and poor prognosis. However, in AML, HSPB1 expression levels are downregulated and are considered a negative prognostic factor, based on hazard ratio analysis. The phosphorylated form of HSPB1 has been shown to inhibit apoptosis and induce autophagy, while reducing cellular iron uptake and lipid ROS production, which may serve protective roles in AML (106).
As an antioxidant enzyme, AIFM2 operates in conjunction with GPX4 and GSH to inhibit phospholipid peroxidation and prevent ferroptosis (95,107). In certain types of cancer, such as cervical cancer and hepatocellular carcinoma, the expression levels of AIFM2 have been associated with a reduction in tumor formation (108). As a crucial rate-limiting enzyme in cholesterol metabolism, SQLE activity is positively correlated with the proliferation and metastasis of various types of cancers and may impact tumor prognosis (109). Its high expression is typically associated with poor prognosis. The enzyme PGD mediates the pentose phosphate pathway and is often upregulated in certain types of tumors, such as glioblastoma and breast cancer. It potentially promotes the proliferation and survival of tumor cells by modifying their energy metabolism (110). ACSF2 is an acyl-CoA synthetase whose role in AML is unknown, but has been found to correlate with prognosis in other diseases. For example, in hepatocellular carcinoma, high expression of ACSF2 is associated with shorter overall survival and relapse-free survival, predicting worsening prognostics. In contrast, in diabetic nephropathy, increased expression of ACSF2 is associated with tubular damage and predicts disease progressibility. The mechanisms and effects of this enzyme in different diseases are still being studied, but its importance in prognosis has attracted widespread attention (96,111). CHAC1 is suggested to regulate ferroptosis by influencing intracellular GSH levels (112). CISD1 participates in intracellular iron accumulation and oxidative damage, and may potentially affect ferroptosis (113). Specifically, CHAC1, as part of the endoplasmic reticulum stress response pathway, induces ferroptosis by regulating glutathione depletion, promoting intracellular iron accumulation and lipid peroxidation. DPP4 has been suggested to regulate ferroptosis by impacting membrane-associated lipid peroxidation processes. GPX, which functions as an antioxidant enzyme, directly inhibits lipid peroxidation and prevents ferroptosis (114).
Twist-related protein 1 (TWIST), as a pivotal factor in cell transformation, plays a crucial role in the process of normal cells becoming cancerous. Studies have reported that its activity can regulate the cell cycle process in AML cells, enhancing their responsiveness to chemotherapy drugs and increasing the sensitivity of AML patients to treatment, ultimately improving prognosis. Research on TWIST1 in AML primarily focuses on laboratory studies conducted in cell and animal models (115). As an unconventional ligand in the Notch signaling pathway, the upregulation of DLL3 may exert a regulatory effect on the growth and division process of AML cells, which in certain cases is associated with improved survival (116). For instance, in SCLC, high expression of DLL3 has been linked to the responsiveness of certain treatments. Specifically, DLL3-targeted therapies, such as antibody-drug conjugates and T-cell engagers, have shown promising efficacy in clinical trials against tumors with high DLL3 expression (117). LGALS1 is commonly associated with the immunomodulatory function of cells. Research has shown that its expression may support AML cells in evading immune system surveillance and may be linked to increased drug resistance, leading to a poor prognosis (118,119).
Studies have confirmed that PHKG2′s role in regulating polyunsaturated fatty acid peroxidation could impact the sensitivity of cells to ferroptosis inducers, such as Erastin, and potentially affect the ferroptosis process (120). HSD17B11, an enzyme that participates in the reduction or oxidation of sex hormones, may be involved in the regulation of ferroptosis in RSL3-resistant cells (121). Six-transmembrane epithelial antigen of prostate 3 (STEAP3), a metal reductase, can convert iron from Fe3+ to Fe2+ and is involved in the transcription of cell death genes and regulation of ferroptosis, particularly through its role in p53-mediated processes (122). HRAS, an important member of the cell signaling network, may enhance the sensitivity of AML patients to cytarabine (123). Through high-throughput drug screening and single-cell genomic analysis, studies have found that HRAS mutations are associated with the sensitivity to certain drugs, such as cytarabine (124). These studies suggest that HRAS mutations may enhance the response of AML cells to cytarabine by altering cell signaling pathways. However, their impact on ferroptosis inducers may vary between different types of cancers. For example, in pancreatic ductal adenocarcinoma, KRAS mutations are the most common early genetic alterations and are closely associated with ferroptosis sensitivity (125). On the other hand, in NSCLC, patients with KRAS mutations show lower responsiveness to ferroptosis inducers (126). ARNTL inhibits ferroptosis by suppressing EGLN2 transcription and activating the pro-survival transcription factor HIF1A, and upregulation of ARNTL can increase susceptibility to anticancer drugs (127). SLC38A1, a mediator of glutamine uptake and lipid peroxidation metabolism, is important for iron apoptosis and high expression levels of SLC38A1 have been associated with a poor prognosis for patients with AML (128).
LPCAT3, a key player in the ferroptosis mechanism of cells, facilitates the incorporation of PUFAs into phospholipids, which are essential substrates for lipid peroxidation in ferroptosis (129). Inhibition of LPCAT3 reduced lipid peroxidation, which lead to reduced sensitivity of cells to ferroptosis inducers, such as RSL3 and Erastin (130). Consequently, the regulation of LPCAT3 may significantly impact the occurrence of ferroptosis in patients with AML and potentially serve as a novel therapeutic target for AML treatment. These findings provide promising research directions for the treatment of AML.
FRGs are a major focus of current research on the prognosis of patients with AML as an independent prognostic factor. Further research is required to determine whether the evaluation of FRGs paired with other dysregulated molecular mechanisms may increase the accuracy of predictive models.
Future perspective and conclusion
In contrast with apoptotic, necrotic and autophagic cell death, ferroptosis is an iron-dependent mode of programmed cell death, more recently identified. Since Dixon et al (12) initially described ferroptosis in 2012, an increasing body of data has indicated that ferroptosis is directly linked to the incidence, progression and inhibition of several diseases, however research remains limited regarding its role in AML (131).
The present review discusses the primary mechanisms of ferroptosis and its role in the prognosis and targeted therapy of AML. In the study of AML, ferroptosis is considered to be a complex process involving several signaling pathways, including the GSH/GPX4 pathway, iron metabolism, lipid metabolism and AMPK signaling. As AML cells can escape ferroptosis through several pathways, future treatment strategies should target multiple pathways to ensure that ferroptosis can effectively occur. Certain existing compounds, such as APR-246 and ATPR, have shown potential in inducing ferroptosis in AML cells, but the interaction of ferroptosis with other cell death pathways, such as autophagy and chemotherapy resistance, should also be considered. Advances in nanotechnology offer novel opportunities to precisely target AML cells, potentially inducing ferroptosis while reducing adverse reactions. Through the establishment of a genetic prognostic risk model, the search for FRGs that are closely related to AML may help predict the prognosis of AML and may improve the clinical application of ferroptosis treatment. However, the current understanding of ferroptosis mechanisms and drug resistance in AML remains incomplete, and the targeting of ferroptosis, through the use of small molecule inhibitors, natural compounds and drug nano-administration, provides novel research directions and therapeutic possibilities for the treatment of AML.
Acknowledgements
Not applicable.
Funding
The present study was funded by the Natural Science Foundation of Shandong Province (grant nos. ZR2022MH310 and ZR2023MH376).
Availability of data and materials
Not applicable.
Authors' contributions
WZ drafted the manuscript. WW, MZ, TZ, HC and RT contributed to the acquisition, analysis and interpretation of data. XF and JW revised the manuscript. All authors read and approved the final manuscript. Data authentication is not applicable.
Ethics approval and consent to participate
Not applicable.
Patient consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
Glossary
Abbreviations
Abbreviations:
GSH |
glutathione |
GPX4 |
glutathione peroxidase 4 |
Nrf2 |
nuclear factor erythroid 2-related factor 2 |
AMP |
adenosine 5′-monophosphate |
AMPK |
AMP-activated protein kinase |
MVA pathway |
mevalonate pathway |
HMG-CoA |
hydroxymethylglutaryl-CoA |
Acetyl-CoA |
acetyl coenzyme A |
IPP |
isopentenyl pyrophosphate |
DMAPP |
dimethylallyl pyrophosphate |
LIP |
labile iron pool |
FPN |
ferroportin |
FTH1 |
ferritin heavy chain 1 |
FT |
ferritin light chain |
TRSP |
selenocysteine-specific transfer RNA |
FSP1 |
ferroptosis suppressor protein 1 |
HO-1 |
heme oxygenase 1 |
SLC25A28 |
solute carrier family 25 member 28 |
TfR1 |
transferrin receptor 1 |
NCOA4 |
nuclear receptor coactivator 4 |
IREB2 |
iron responsive element binding protein 2 |
HSPB1 |
heat shock protein family B (small) member 1 |
STEAP3 |
six-transmembrane epithelial antigen of prostate 3 |
DMT1 |
divalent metal transporter 1 |
Keap1 |
ECH associated protein |
SAT1 |
spermine N1-acetyltransferase 1 |
ALOX15 |
arachidonate-15-lipoxygenase |
GLS2 |
glutaminase |
AA |
arachidonic acid |
AdA |
adrenoyl derivatives |
PE-AA/AdA |
phosphatidylethanolamines |
PUFAs |
polyunsaturated fatty acids |
BECN1 |
beclin 1 |
SLC7A11 |
solute carrier family 7 member 11 |
ROS |
reactive oxygen species |
APR-246 |
Eprenetapopt |
ALDH3A2 |
aldehyde dehydrogenase 3 family member A2 |
circKDM4C |
circular RNA derived from the KDM4C gene |
GCMNPs |
poly(lactic acid)-glycolic acid-encapsulated glycyrrhetinic acids |
TYP |
typhaneoside |
HMOX1 |
heme oxygenase 1 |
HMGB1 |
high mobility group box 1 |
DHA |
dihydroartemisinin |
GNPIPP12MA |
glutathione-bioimprinted nanoparticles targeting N6-methyladenosine FTO demethylase |
GnRA-CSP12 |
gold nanorods functionalized with chitosan and a 12-mer peptide12 |
RSL3 |
RAS-selective lethal |
ATRA |
all-trans retinoic acid |
ATPR |
4-amino-2-trifluoromethyl-phenyl retinate |
FRG |
ferroptosis-related genes |
DNAJB6 |
DNAJ heat shock protein family member B6 |
TWIST |
twist-related protein 1 |
LPCAT3 |
lysophospholipid acyltransferase |
References
Medinger M, Heim D, Halter JP, Lengerke C and Passweg JR: Diagnosis and therapy of acute myeloid leukemia. Ther Umsch. 76:481–486. 2019.(In German). View Article : Google Scholar : PubMed/NCBI | |
Pelcovits A and Niroula R: Acute myeloid leukemia: A review. R I Med J. 103:38–40. 2020. | |
Shimony S, Stahl M and Stone RM: Acute myeloid leukemia: 2023 update on diagnosis, risk-stratification, and management. Am J Hematol. 98:502–526. 2023. View Article : Google Scholar : PubMed/NCBI | |
Ren Y, Mao X, Xu H, Dang Q, Weng S, Zhang Y, Chen S, Liu S, Ba Y, Zhou Z, et al: Ferroptosis and EMT: Key targets for combating cancer progression and therapy resistance. Cell Mol Life Sci. 80:2632023. View Article : Google Scholar : PubMed/NCBI | |
Zhang C, Liu X, Jin S, Chen Y and Guo R: Ferroptosis in cancer therapy: A novel approach to reversing drug resistance. Mol Cancer. 21:472022. View Article : Google Scholar : PubMed/NCBI | |
Mou Y, Wang J, Wu J, He D, Zhang C, Duan C and Li B: Ferroptosis, a new form of cell death: Opportunities and challenges in cancer. J Hematol Oncol. 12:342019. View Article : Google Scholar : PubMed/NCBI | |
Lei G, Zhuang L and Gan B: Targeting ferroptosis as a vulnerability in cancer. Nat Rev Cancer. 22:381–396. 2022. View Article : Google Scholar : PubMed/NCBI | |
Liang C, Zhang X, Yang M and Dong X: Recent progress in ferroptosis inducers for cancer therapy. Adv Mater. 31:e19041972019. View Article : Google Scholar : PubMed/NCBI | |
Liang D, Minikes AM and Jiang X: Ferroptosis at the intersection of lipid metabolism and cellular signaling. Mol Cell. 82:2215–2227. 2022. View Article : Google Scholar : PubMed/NCBI | |
Balihodzic A, Prinz F, Dengler MA, Calin GA, Jost PJ and Pichler M: Non-coding RNAs and ferroptosis: Potential implications for cancer therapy. Cell Death Differ. 29:1094–1106. 2022. View Article : Google Scholar : PubMed/NCBI | |
Hirschhorn T and Stockwell BR: The development of the concept of ferroptosis. Free Radic Biol Med. 133:130–143. 2019. View Article : Google Scholar : PubMed/NCBI | |
Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, Patel DN, Bauer AJ, Cantley AM, Yang WS, et al: Ferroptosis: An iron-dependent form of nonapoptotic cell death. Cell. 149:1060–1072. 2012. View Article : Google Scholar : PubMed/NCBI | |
Li J, Cao F, Yin HL, Huang ZJ, Lin ZT, Mao N, Sun B and Wang G: Ferroptosis: Past, present and future. Cell Death Dis. 11:882020. View Article : Google Scholar : PubMed/NCBI | |
Stockwell BR, Jiang X and Gu W: Emerging mechanisms and disease relevance of ferroptosis. Trends Cell Biol. 30:478–490. 2020. View Article : Google Scholar : PubMed/NCBI | |
Chen X, Li J, Kang R, Klionsky DJ and Tang D: Ferroptosis: Machinery and regulation. Autophagy. 17:2054–2081. 2021. View Article : Google Scholar : PubMed/NCBI | |
Su Y, Zhao B, Zhou L, Zhang Z, Shen Y, Lv H, AlQudsy LHH and Shang P: Ferroptosis, a novel pharmacological mechanism of anti-cancer drugs. Cancer Lett. 483:127–136. 2020. View Article : Google Scholar : PubMed/NCBI | |
Miotto G, Rossetto M, Di Paolo ML, Orian L, Venerando R, Roveri A, Vučković AM, Bosello Travain V, Zaccarin M, Zennaro L, et al: Insight into the mechanism of ferroptosis inhibition by ferrostatin-1. Redox Biol. 28:1013282020. View Article : Google Scholar : PubMed/NCBI | |
Xu T, Ding W, Ji X, Ao X, Liu Y, Yu W and Wang J: Molecular mechanisms of ferroptosis and its role in cancer therapy. J Cell Mol Med. 23:4900–4912. 2019. View Article : Google Scholar : PubMed/NCBI | |
Tang D, Chen X, Kang R and Kroemer G: Ferroptosis: Molecular mechanisms and health implications. Cell Res. 31:107–125. 2021. View Article : Google Scholar : PubMed/NCBI | |
Liu Y, Wan Y, Jiang Y, Zhang L and Cheng W: GPX4: The hub of lipid oxidation, ferroptosis, disease and treatment. Biochim Biophys Acta Rev Cancer. 1878:1888902023. View Article : Google Scholar : PubMed/NCBI | |
Forcina GC and Dixon SJ: GPX4 at the crossroads of lipid homeostasis and ferroptosis. Proteomics. 19:e18003112019. View Article : Google Scholar : PubMed/NCBI | |
Xing K, Bian X, Shi D, Dong S, Zhou H, Xiao S, Bai J and Wu W: miR-612 Enhances RSL3-Induced ferroptosis of hepatocellular carcinoma cells via mevalonate pathway. J Hepatocell Carcinoma. 10:2173–2185. 2023. View Article : Google Scholar : PubMed/NCBI | |
Ou M, Jiang Y, Ji Y, Zhou Q, Du Z, Zhu H and Zhou Z: Role and mechanism of ferroptosis in neurological diseases. Mol Metab. 61:1015022022. View Article : Google Scholar : PubMed/NCBI | |
Noe R, Inglese N, Romani P, Serafini T, Paoli C, Calciolari B, Fantuz M, Zamborlin A, Surdo NC, Spada V, et al: Organic Selenium induces ferroptosis in pancreatic cancer cells. Redox Biol. 68:1029622023. View Article : Google Scholar : PubMed/NCBI | |
Zheng J and Conrad M: The metabolic underpinnings of ferroptosis. Cell Metab. 32:920–937. 2020. View Article : Google Scholar : PubMed/NCBI | |
Xia J, Si H, Yao W, Li C, Yang G, Tian Y and Hao C: Research progress on the mechanism of ferroptosis and its clinical application. Exp Cell Res. 409:1129322021. View Article : Google Scholar : PubMed/NCBI | |
Liu J, Zhang C, Wang J, Hu W and Feng Z: The regulation of ferroptosis by tumor suppressor p53 and its pathway. Int J Mol Sci. 21:83872020. View Article : Google Scholar : PubMed/NCBI | |
Lei P, Bai T and Sun Y: Mechanisms of ferroptosis and relations with regulated cell death: A Review. Front Physiol. 10:1392019. View Article : Google Scholar : PubMed/NCBI | |
Xu R, Wang W and Zhang W: Ferroptosis and the bidirectional regulatory factor p53. Cell Death Discov. 9:1972023. View Article : Google Scholar : PubMed/NCBI | |
Wang H, Guo M, Wei H and Chen Y: Targeting p53 pathways: Mechanisms, structures, and advances in therapy. Signal Transduct Target Ther. 8:922023. View Article : Google Scholar : PubMed/NCBI | |
Park E and Chung SW: ROS-mediated autophagy increases intracellular iron levels and ferroptosis by ferritin and transferrin receptor regulation. Cell Death Dis. 10:8222019. View Article : Google Scholar : PubMed/NCBI | |
Stockwell BR: Ferroptosis turns 10: Emerging mechanisms, physiological functions, and therapeutic applications. Cell. 185:2401–2421. 2022. View Article : Google Scholar : PubMed/NCBI | |
Fuhrmann DC and Brune B: A graphical journey through iron metabolism, microRNAs, and hypoxia in ferroptosis. Redox Biol. 54:1023652022. View Article : Google Scholar : PubMed/NCBI | |
Bayir H, Dixon SJ, Tyurina YY, Kellum JA and Kagan VE: Ferroptotic mechanisms and therapeutic targeting of iron metabolism and lipid peroxidation in the kidney. Nat Rev Nephrol. 19:315–336. 2023. View Article : Google Scholar : PubMed/NCBI | |
Sun X, Ou Z, Chen R, Niu X, Chen D, Kang R and Tang D: Activation of the p62-Keap1-NRF2 pathway protects against ferroptosis in hepatocellular carcinoma cells. Hepatology. 63:173–184. 2016. View Article : Google Scholar : PubMed/NCBI | |
Li D and Li Y: The interaction between ferroptosis and lipid metabolism in cancer. Signal Transduct Target Ther. 5:1082020. View Article : Google Scholar : PubMed/NCBI | |
Zheng XJ, Chen WL, Yi J, Li W, Liu JY, Fu WQ, Ren LW, Li S, Ge BB, Yang YH, et al: Apolipoprotein C1 promotes glioblastoma tumorigenesis by reducing KEAP1/NRF2 and CBS-regulated ferroptosis. Acta Pharmacol Sin. 43:2977–2992. 2022. View Article : Google Scholar : PubMed/NCBI | |
Zheng XJ, Chen WL, Yi J, Li W, Liu JY, Fu WQ, Ren LW, Li S, Ge BB, Yang YH, et al: Author Correction: Apolipoprotein C1 promotes glioblastoma tumorigenesis by reducing KEAP1/NRF2 and CBS-regulated ferroptosis. Acta Pharmacol Sin. May 13–2024.doi: 10.1038/s41401-024-01271-2 (Epub ahead of print). | |
Zimta AA, Cenariu D, Irimie A, Magdo L, Nabavi SM, Atanasov AG and Berindan-Neagoe I: The role of Nrf2 activity in cancer development and progression. Cancers (Basel). 11:17552019. View Article : Google Scholar : PubMed/NCBI | |
Grignano E, Birsen R, Chapuis N and Bouscary D: From iron chelation to overload as a therapeutic strategy to induce ferroptosis in leukemic cells. Front Oncol. 10:5865302020. View Article : Google Scholar : PubMed/NCBI | |
Zeng F, Nijiati S, Tang L, Ye J, Zhou Z and Chen X: Ferroptosis detection: From approaches to applications. Angew Chem Int Ed Engl. 62:e2023003792023. View Article : Google Scholar : PubMed/NCBI | |
Chen X, Kang R, Kroemer G and Tang D: Broadening horizons: The role of ferroptosis in cancer. Nat Rev Clin Oncol. 18:280–296. 2021. View Article : Google Scholar : PubMed/NCBI | |
Koppula P, Zhuang L and Gan B: Cystine transporter SLC7A11/xCT in cancer: Ferroptosis, nutrient dependency, and cancer therapy. Protein Cell. 12:599–620. 2021. View Article : Google Scholar : PubMed/NCBI | |
Sun X, Ou Z, Xie M, Kang R, Fan Y, Niu X, Wang H, Cao L and Tang D: HSPB1 as a novel regulator of ferroptotic cancer cell death. Oncogene. 34:5617–5625. 2015. View Article : Google Scholar : PubMed/NCBI | |
Liu Y and Gu W: p53 in ferroptosis regulation: The new weapon for the old guardian. Cell Death Differ. 29:895–910. 2022. View Article : Google Scholar : PubMed/NCBI | |
Gong D, Chen M, Wang Y, Shi J and Hou Y: Role of ferroptosis on tumor progression and immunotherapy. Cell Death Discov. 8:4272022. View Article : Google Scholar : PubMed/NCBI | |
Liu Y and Gu W: The complexity of p53-mediated metabolic regulation in tumor suppression. Semin Cancer Biol. 85:4–32. 2022. View Article : Google Scholar : PubMed/NCBI | |
Gao Y, Zhang H, Wang J, Li F, Li X, Li T, Wang C, Li L, Peng R, Liu L, et al: Annexin A5 ameliorates traumatic brain injury-induced neuroinflammation and neuronal ferroptosis by modulating the NF-kB/HMGB1 and Nrf2/HO-1 pathways. Int Immunopharmacol. 114:1096192023. View Article : Google Scholar : PubMed/NCBI | |
Ursini F and Maiorino M: Lipid peroxidation and ferroptosis: The role of GSH and GPx4. Free Radic Biol Med. 152:175–185. 2020. View Article : Google Scholar : PubMed/NCBI | |
Pope LE and Dixon SJ: Regulation of ferroptosis by lipid metabolism. Trends Cell Biol. 33:1077–1087. 2023. View Article : Google Scholar : PubMed/NCBI | |
Zhao L, Zhou X, Xie F and Zhang L, Yan H, Huang J, Zhang C, Zhou F, Chen J and Zhang L: Ferroptosis in cancer and cancer immunotherapy. Cancer Commun (Lond). 42:88–116. 2022. View Article : Google Scholar : PubMed/NCBI | |
Lee H, Zandkarimi F, Zhang Y, Meena JK, Kim J, Zhuang L, Tyagi S, Ma L, Westbrook TF, Steinberg GR, et al: Energy-stress-mediated AMPK activation inhibits ferroptosis. Nat Cell Biol. 22:225–234. 2020. View Article : Google Scholar : PubMed/NCBI | |
Song X, Zhu S, Chen P, Hou W, Wen Q, Liu J, Xie Y, Liu J, Klionsky DJ, Kroemer G, et al: AMPK-Mediated BECN1 phosphorylation promotes ferroptosis by directly blocking system Xc-Activity. Curr Biol. 28:2388–2399. 2018. View Article : Google Scholar : PubMed/NCBI | |
Winer ES: Secondary acute myeloid leukemia: A primary challenge of diagnosis and treatment. Hematol Oncol Clin North Am. 34:449–463. 2020. View Article : Google Scholar : PubMed/NCBI | |
Su Y, Zhao B, Zhou L, Zhang Z, Shen Y, Lv H, AlQudsy LHH and Shang P: Ferroptosis, a novel pharmacological mechanism of anti-cancer drugs. Cancer Lett. 483:127–136. 2020. View Article : Google Scholar : PubMed/NCBI | |
Farge T, Saland E, de Toni F, Aroua N, Hosseini M, Perry R, Bosc C, Sugita M, Stuani L, Fraisse M, et al: Chemotherapy-Resistant human acute myeloid leukemia cells are not enriched for leukemic stem cells but require oxidative metabolism. Cancer Discov. 7:716–735. 2017. View Article : Google Scholar : PubMed/NCBI | |
Akiyama H, Zhao R, Ostermann LB, Li Z, Tcheng M, Yazdani SJ, Moayed A, Pryor ML II, Slngh S, Baran N, et al: Correction: Mitochondrial regulation of GPX4 inhibition-mediated ferroptosis in acute myeloid leukemia. Leukemia. 38:9262024. View Article : Google Scholar : PubMed/NCBI | |
Auberger P, Favreau C, Savy C, Jacquel A and Robert G: Emerging role of glutathione peroxidase 4 in myeloid cell lineage development and acute myeloid leukemia. Cell Mol Biol Lett. 29:982024. View Article : Google Scholar : PubMed/NCBI | |
Zhong X, Zhang Z, Shen H, Xiong Y, Shah YM, Liu Y, Fan XG and Rui L: Hepatic NF-κB-Inducing kinase and inhibitor of NF-κB kinase subunit α promote liver oxidative stress, ferroptosis, and liver injury. Hepatol Commun. 5:1704–1720. 2021. View Article : Google Scholar : PubMed/NCBI | |
Rushworth SA, Zaitseva L, Murray MY, Shah NM, Bowles KM and MacEwan DJ: The high Nrf2 expression in human acute myeloid leukemia is driven by NF-κB and underlies its chemo-resistance. Blood. 120:5188–5198. 2012. View Article : Google Scholar : PubMed/NCBI | |
Akiyama H, Zhao R, Ostermann LB, Li Z, Tcheng M, Yazdani SJ, Moayed A, Pryor ML II, Slngh S, Baran N, et al: Mitochondrial regulation of GPX4 inhibition-mediated ferroptosis in acute myeloid leukemia. Leukemia. 38:729–740. 2024. View Article : Google Scholar : PubMed/NCBI | |
Pabst T, Kortz L, Fiedler GM, Ceglarek U, Idle JR and Beyoğlu D: The plasma lipidome in acute myeloid leukemia at diagnosis in relation to clinical disease features. BBA Clin. 7:105–114. 2017. View Article : Google Scholar : PubMed/NCBI | |
Strickland SA and Vey N: Diagnosis and treatment of therapy-related acute myeloid leukemia. Crit Rev Oncol Hematol. 171:1036072022. View Article : Google Scholar : PubMed/NCBI | |
Roberts MD, Langston AA and Heffner LJ: Acute myeloid leukemia in young adults: Does everyone need a transplant? J Oncol Pract. 15:315–320. 2019. View Article : Google Scholar | |
Barriga F, Ramirez P, Wietstruck A and Rojas N: Hematopoietic stem cell transplantation: Clinical use and perspectives. Biol Res. 45:307–316. 2012. View Article : Google Scholar : PubMed/NCBI | |
Birsen R, Larrue C, Decroocq J, Johnson N, Guiraud N, Gotanegre M, Cantero-Aguilar L, Grignano E, Huynh T, Fontenay M, et al: APR-246 induces early cell death by ferroptosis in acute myeloid leukemia. Haematologica. 107:403–416. 2022. View Article : Google Scholar : PubMed/NCBI | |
Yusuf RZ, Saez B, Sharda A, van Gastel N, Yu VWC, Baryawno N, Scadden EW, Acharya S, Chattophadhyay S, Huang C, et al: Aldehyde dehydrogenase 3a2 protects AML cells from oxidative death and the synthetic lethality of ferroptosis inducers. Blood. 136:1303–1316. 2020. View Article : Google Scholar : PubMed/NCBI | |
Li Q, Su R, Bao X, Cao K, Du Y, Wang N, Wang J, Xing F, Yan F, Huang K and Feng S: Glycyrrhetinic acid nanoparticles combined with ferrotherapy for improved cancer immunotherapy. Acta Biomater. 144:109–120. 2022. View Article : Google Scholar : PubMed/NCBI | |
Cao K, Du Y, Bao X, Han M, Su R, Pang J, Liu S, Shi Z, Yan F and Feng S: Glutathione-Bioimprinted nanoparticles targeting of N6-methyladenosine FTO Demethylase as a strategy against leukemic stem cells. Small. 18:e21065582022. View Article : Google Scholar : PubMed/NCBI | |
Peng X, Zhang MQ, Conserva F, Hosny G, Selivanova G, Bykov VJ, Arnér ES and Wiman KG: APR-246/PRIMA-1MET inhibits thioredoxin reductase 1 and converts the enzyme to a dedicated NADPH oxidase. Cell Death Dis. 4:e8812013. View Article : Google Scholar : PubMed/NCBI | |
Ali D, Jonsson-Videsater K, Deneberg S, Bengtzén S, Nahi H, Paul C and Lehmann S: APR-246 exhibits anti-leukemic activity and synergism with conventional chemotherapeutic drugs in acute myeloid leukemia cells. Eur J Haematol. 86:206–215. 2011. View Article : Google Scholar : PubMed/NCBI | |
Sallman DA, DeZern AE, Garcia-Manero G, Steensma DP, Roboz GJ, Sekeres MA, Cluzeau T, Sweet KL, McLemore A, McGraw KL, et al: Eprenetapopt (APR-246) and azacitidine in TP53-Mutant myelodysplastic syndromes. J Clin Oncol. 39:1584–1594. 2021. View Article : Google Scholar : PubMed/NCBI | |
Wang Y, Tang B, Zhu J, Yu J, Hui J, Xia S and Ji J: Emerging mechanisms and targeted therapy of ferroptosis in neurological diseases and Neuro-oncology. Int J Biol Sci. 18:4260–4274. 2022. View Article : Google Scholar : PubMed/NCBI | |
Dong LH, Huang JJ, Zu P, Liu J, Gao X, Du JW and Li YF: CircKDM4C upregulates P53 by sponging hsa-let-7b-5p to induce ferroptosis in acute myeloid leukemia. Environ Toxicol. 36:1288–1302. 2021. View Article : Google Scholar : PubMed/NCBI | |
Kang R, Kroemer G and Tang D: The tumor suppressor protein p53 and the ferroptosis network. Free Radic Biol Med. 133:162–168. 2019. View Article : Google Scholar : PubMed/NCBI | |
Yu Y, Meng Y, Xu X, Tong T, He C, Wang L, Wang K, Zhao M, You X, Zhang W, et al: A Ferroptosis-inducing and leukemic cell-Targeting drug nanocarrier formed by Redox-Responsive cysteine polymer for acute myeloid leukemia therapy. ACS Nano. 17:3334–3345. 2023. View Article : Google Scholar : PubMed/NCBI | |
Lang X, Green MD, Wang W, Yu J, Choi JE, Jiang L, Liao P, Zhou J, Zhang Q, Dow A, et al: Radiotherapy and immunotherapy promote tumoral lipid oxidation and ferroptosis via synergistic repression of SLC7A11. Cancer Discov. 9:1673–1685. 2019. View Article : Google Scholar : PubMed/NCBI | |
Xu H, Ye D, Ren M, Zhang H and Bi F: Ferroptosis in the tumor microenvironment: Perspectives for immunotherapy. Trends Mol Med. 27:856–867. 2021. View Article : Google Scholar : PubMed/NCBI | |
Su R, Dong L, Li Y, Gao M, Han L, Wunderlich M, Deng X, Li H, Huang Y, Gao L, et al: Targeting FTO suppresses cancer stem cell maintenance and immune evasion. Cancer Cell. 38:79–96. 2020. View Article : Google Scholar : PubMed/NCBI | |
Du Y, Han M, Cao K, Li Q, Pang J, Dou L, Liu S, Shi Z, Yan F and Feng S: Gold nanorods exhibit intrinsic therapeutic activity via controlling N6-methyladenosine-based Epitranscriptomics in acute myeloid leukemia. ACS Nano. 15:17689–17704. 2021. View Article : Google Scholar : PubMed/NCBI | |
Wen Q, Liu J, Kang R, Zhou B and Tang D: The release and activity of HMGB1 in ferroptosis. Biochem Biophys Res Commun. 510:278–283. 2019. View Article : Google Scholar : PubMed/NCBI | |
Chen GQ, Benthani FA, Wu J, Liang D, Bian ZX and Jiang X: Artemisinin compounds sensitize cancer cells to ferroptosis by regulating iron homeostasis. Cell Death Differ. 27:242–254. 2020. View Article : Google Scholar : PubMed/NCBI | |
Zhu HY, Huang ZX, Chen GQ, Sheng F and Zheng YS: Typhaneoside prevents acute myeloid leukemia (AML) through suppressing proliferation and inducing ferroptosis associated with autophagy. Biochem Biophys Res Commun. 516:1265–1271. 2019. View Article : Google Scholar : PubMed/NCBI | |
Du Y, Bao J, Zhang MJ, Li LL, Xu XL, Chen H, Feng YB, Peng XQ and Chen FH: Targeting ferroptosis contributes to ATPR-induced AML differentiation via ROS-autophagy-lysosomal pathway. Gene. 755:1448892020. View Article : Google Scholar : PubMed/NCBI | |
Bruedigam C, Porter AH, Song A, Vroeg In de Wei G, Stoll T, Straube J, Cooper L, Cheng G, Kahl VFS, Sobinoff AP, et al: Imetelstat-mediated alterations in fatty acid metabolism to induce ferroptosis as a therapeutic strategy for acute myeloid leukemia. Nat Cancer. 5:47–65. 2024. View Article : Google Scholar : PubMed/NCBI | |
Lai X, Sun Y, Zhang X, Wang D, Wang J, Wang H, Zhao Y, Liu X, Xu X, Song H, et al: Honokiol induces ferroptosis by upregulating HMOX1 in acute myeloid leukemia cells. Front Pharmacol. 13:8977912022. View Article : Google Scholar : PubMed/NCBI | |
Gan B: How erastin assassinates cells by ferroptosis revealed. Protein Cell. 14:84–86. 2023.PubMed/NCBI | |
Yu Y, Xie Y, Cao L, Yang L, Yang M, Lotze MT, Zeh HJ, Kang R and Tang D: The ferroptosis inducer erastin enhances sensitivity of acute myeloid leukemia cells to chemotherapeutic agents. Mol Cell Oncol. 2:e10545492015. View Article : Google Scholar : PubMed/NCBI | |
Ye F, Chai W, Xie M, Yang M, Yu Y, Cao L and Yang L: HMGB1 regulates erastin-induced ferroptosis via RAS-JNK/p38 signaling in HL-60/NRAS(Q61L) cells. Am J Cancer Res. 9:730–739. 2019.PubMed/NCBI | |
Du J, Wang T, Li Y, Zhou Y, Wang X, Yu X, Ren X, An Y, Wu Y, Sun W, et al: DHA inhibits proliferation and induces ferroptosis of leukemia cells through autophagy dependent degradation of ferritin. Free Radic Biol Med. 131:356–369. 2019. View Article : Google Scholar : PubMed/NCBI | |
Nishizawa H, Yamanaka M and Igarashi K: Ferroptosis: Regulation by competition between NRF2 and BACH1 and propagation of the death signal. FEBS J. 290:1688–1704. 2023. View Article : Google Scholar : PubMed/NCBI | |
Du Y, Zhang MJ, Li LL, Xu XL, Chen H, Feng YB, Li Y, Peng XQ and Chen FH: ATPR triggers acute myeloid leukaemia cells differentiation and cycle arrest via the RARalpha/LDHB/ERK-glycolysis signalling axis. J Cell Mol Med. 24:6952–6965. 2020. View Article : Google Scholar : PubMed/NCBI | |
Pelcovits A and Niroula R: Acute myeloid leukemia: A review. R I Med J (2013). 103:38–40. 2020.PubMed/NCBI | |
Yin Z, Li F, Zhou Q, Zhu J, Liu Z, Huang J, Shen H, Ou R, Zhu Y, Zhang Q and Liu S: A ferroptosis-related gene signature and immune infiltration patterns predict the overall survival in acute myeloid leukemia patients. Front Mol Biosci. 9:9597382022. View Article : Google Scholar : PubMed/NCBI | |
Prada-Arismendy J, Arroyave JC and Rothlisberger S: Molecular biomarkers in acute myeloid leukemia. Blood Rev. 31:63–76. 2017. View Article : Google Scholar : PubMed/NCBI | |
Han C, Zheng J, Li F, Guo W and Cai C: Novel prognostic signature for acute myeloid leukemia: Bioinformatics analysis of combined CNV-driven and ferroptosis-related genes. Front Genet. 13:8494372022. View Article : Google Scholar : PubMed/NCBI | |
Song Y, Tian S, Zhang P, Zhang N, Shen Y and Deng J: Construction and validation of a novel Ferroptosis-Related prognostic model for acute myeloid leukemia. Front Genet. 12:7086992022. View Article : Google Scholar : PubMed/NCBI | |
Wei J, Xie Q, Liu X, Wan C, Wu W, Fang K, Yao Y, Cheng P, Deng D and Liu Z: Identification the prognostic value of glutathione peroxidases expression levels in acute myeloid leukemia. Ann Transl Med. 8:6782020. View Article : Google Scholar : PubMed/NCBI | |
Chen Z, Wu T, Yan Z and Zhang M: Identification and validation of an 11-Ferroptosis related gene signature and its correlation with immune checkpoint molecules in glioma. Front Cell Dev Biol. 9:6525992021. View Article : Google Scholar : PubMed/NCBI | |
Huang X, Zhou D, Ye X and Jin J: A novel ferroptosis-related gene signature can predict prognosis and influence immune microenvironment in acute myeloid leukemia. Bosn J Basic Med Sci. 22:608–628. 2021.PubMed/NCBI | |
Zhu L, Yang F, Wang L, Dong L, Huang Z, Wang G, Chen G and Li Q: Identification the ferroptosis-related gene signature in patients with esophageal adenocarcinoma. Cancer Cell Int. 21:1242021. View Article : Google Scholar : PubMed/NCBI | |
Zhang X, Zhang X, Liu K, Li W, Wang J, Liu P and Ma W: HIVEP3 cooperates with ferroptosis gene signatures to confer adverse prognosis in acute myeloid leukemia. Cancer Med. 11:5050–5065. 2022. View Article : Google Scholar : PubMed/NCBI | |
Jiang B, Zhao Y, Shi M, Song L, Wang Q, Qin Q, Song X, Wu S, Fang Z and Liu X: DNAJB6 promotes ferroptosis in esophageal squamous cell carcinoma. Dig Dis Sci. 65:1999–2008. 2020. View Article : Google Scholar : PubMed/NCBI | |
Meng E, Shevde LA and Samant RS: Retraction: Emerging roles and underlying molecular mechanisms of DNAJB6 in cancer. Oncotarget. 14:6692023. View Article : Google Scholar : PubMed/NCBI | |
Liang Y, Wang Y, Zhang Y, Ye F, Luo D, Li Y, Jin Y, Han D, Wang Z, Chen B, et al: HSPB1 facilitates chemoresistance through inhibiting ferroptotic cancer cell death and regulating NF-κB signaling pathway in breast cancer. Cell Death Dis. 14:4342023. View Article : Google Scholar : PubMed/NCBI | |
Yan XS, Sun YJ, Du J, Niu WY, Qiao H and Yin XC: Effects of ferroptosis-related gene HSPB1 on acute myeloid leukemia. Int J Lab Hematol. June 2–2024.(Epub ahead of print). View Article : Google Scholar | |
Ma Z, Ye W, Huang X, Li X, Li F, Lin X, Hu C, Wang J, Jin J, Zhu B and Huang J: The ferroptosis landscape in acute myeloid leukemia. Aging (Albany NY). 15:13486–13503. 2023. View Article : Google Scholar : PubMed/NCBI | |
Guo S, Li F, Liang Y, Zheng Y, Mo Y, Zhao D, Jiang Z, Cui M, Qi L, Chen J, et al: AIFM2 promotes hepatocellular carcinoma metastasis by enhancing mitochondrial biogenesis through activation of SIRT1/PGC-1α signaling. Oncogenesis. 12:462023. View Article : Google Scholar : PubMed/NCBI | |
Sun Q, Liu D, Cui W, Cheng H, Huang L, Zhang R, Gu J, Liu S, Zhuang X, Lu Y, et al: Cholesterol mediated ferroptosis suppression reveals essential roles of Coenzyme Q and squalene. Commun Biol. 6:11082023. View Article : Google Scholar : PubMed/NCBI | |
Shi J, Wu P, Sheng L, Sun W and Zhang H: Ferroptosis-related gene signature predicts the prognosis of papillary thyroid carcinoma. Cancer Cell Int. 21:6692021. View Article : Google Scholar : PubMed/NCBI | |
Song Y, Tian S, Zhang P, Zhang N, Shen Y and Deng J: Construction and validation of a novel Ferroptosis-Related Prognostic model for acute myeloid leukemia. Front Genet. 12:7086992021. View Article : Google Scholar : PubMed/NCBI | |
Dixon SJ, Patel DN, Welsch M, Skouta R, Lee ED, Hayano M, Thomas AG, Gleason CE, Tatonetti NP, Slusher BS and Stockwell BR: Pharmacological inhibition of Cystine-glutamate exchange induces endoplasmic reticulum stress and ferroptosis. Elife. 3:e025232014. View Article : Google Scholar : PubMed/NCBI | |
Zhang X, Peng T, Li C, Ai C, Wang X, Lei X, Li G and Li T: Inhibition of CISD1 alleviates mitochondrial dysfunction and ferroptosis in mice with acute lung injury. Int Immunopharmacol. 130:1116852024. View Article : Google Scholar : PubMed/NCBI | |
Xie Y, Zhu S, Song X, Sun X, Fan Y, Liu J, Zhong M, Yuan H, Zhang L, Billiar TR, et al: The tumor suppressor p53 limits ferroptosis by blocking DPP4 activity. Cell Rep. 20:1692–1704. 2017. View Article : Google Scholar : PubMed/NCBI | |
Zhang L, Song A, Yang QC, Li SJ, Wang S, Wan SC, Sun J, Kwok RTK, Lam JWY, Deng H, et al: Integration of AIEgens into covalent organic frameworks for pyroptosis and ferroptosis primed cancer immunotherapy. Nat Commun. 14:53552023. View Article : Google Scholar : PubMed/NCBI | |
Wang J, Zhuo Z, Wang Y, Yang S, Chen J, Wang Y, Geng S, Li M, Du X, Lai P, et al: Identification and validation of a prognostic Risk-scoring model based on Ferroptosis-associated cluster in acute myeloid leukemia. Front Cell Dev Biol. 9:8002672021. View Article : Google Scholar : PubMed/NCBI | |
Rudin CM, Reck M, Johnson ML, Blackhall F, Hann CL, Yang JC, Bailis JM, Bebb G, Goldrick A, Umejiego J and Paz-Ares L: Emerging therapies targeting the delta-like ligand 3 (DLL3) in small cell lung cancer. J Hematol Oncol. 16:662023. View Article : Google Scholar : PubMed/NCBI | |
Ruvolo PP, Ma H, Ruvolo VR, Zhang X, Post SM and Andreeff M: LGALS1 acts as a pro-survival molecule in AML. Biochim Biophys Acta Mol Cell Res. 1867:1187852020. View Article : Google Scholar : PubMed/NCBI | |
Sun J, Lu P, Guan S and Liu S: Heterogeneity analysis of pancreatic cancer and identification of molecular subtypes of tumor cells based on CEACAM5, LGALS1 and CENPF gene expression. Nan Fang Yi Ke Da Xue Xue Bao. 43:1567–1576. 2023.(In Chinese). PubMed/NCBI | |
Zhu W, Liu D, Lu Y, Sun J, Zhu J, Xing Y, Ma X, Wang Y, Ji M and Jia Y: PHKG2 regulates RSL3-induced ferroptosis in Helicobacter pylori related gastric cancer. Arch Biochem Biophys. 740:1095602023. View Article : Google Scholar : PubMed/NCBI | |
Sabatier M, Birsen R, Lauture L, Mouche S, Angelino P, Dehairs J, Goupille L, Boussaid I, Heiblig M, Boet E, et al: C/EBPα confers dependence to fatty acid anabolic pathways and vulnerability to lipid oxidative Stress-Induced ferroptosis in FLT3-mutant leukemia. Cancer Discov. 13:1720–1747. 2023. View Article : Google Scholar : PubMed/NCBI | |
Chen X, Hu S, Han Y, Cai Y, Lu T, Hu X, Chu Y, Zhou X and Wang X: Ferroptosis-related STEAP3 acts as predictor and regulator in diffuse large B cell lymphoma through immune infiltration. Clin Exp Med. 23:2601–2617. 2023. View Article : Google Scholar : PubMed/NCBI | |
Dai E, Han L, Liu J, Xie Y, Zeh HJ, Kang R, Bai L and Tang D: Ferroptotic damage promotes pancreatic tumorigenesis through a TMEM173/STING-dependent DNA sensor pathway. Nat Commun. 11:63392020. View Article : Google Scholar : PubMed/NCBI | |
Sadeghi M, Moslehi A, Kheiry H, Kiani FK, Zarei A, Khodakarami A, Karpisheh V, Masjedi A, Rahnama B, Hojjat-Farsangi M, et al: The sensitivity of acute myeloid leukemia cells to cytarabine is increased by suppressing the expression of Heme oxygenase-1 and hypoxia-inducible factor 1-alpha. Cancer Cell Int. 24:2172024. View Article : Google Scholar : PubMed/NCBI | |
Bartolacci C, Andreani C, El-Gammal Y and Scaglioni PP: Lipid metabolism regulates oxidative stress and ferroptosis in RAS-Driven cancers: A perspective on cancer progression and therapy. Front Mol Biosci. 8:7066502021. View Article : Google Scholar : PubMed/NCBI | |
Diao J, Jia Y, Dai E, Liu J, Kang R, Tang D, Han L, Zhong Y and Meng L: Ferroptotic therapy in cancer: Benefits, side effects, and risks. Mol Cancer. 23:892024. View Article : Google Scholar : PubMed/NCBI | |
Chen X, Song X, Li J, Zhang R, Yu C, Zhou Z, Liu J, Liao S, Klionsky DJ, Kroemer G, et al: Identification of HPCAL1 as a specific autophagy receptor involved in ferroptosis. Autophagy. 19:54–74. 2023. View Article : Google Scholar : PubMed/NCBI | |
Zhang H and Sun C, Sun Q, Li Y, Zhou C and Sun C: Susceptibility of acute myeloid leukemia cells to ferroptosis and evasion strategies. Front Mol Biosci. 10:12757742023. View Article : Google Scholar : PubMed/NCBI | |
Liu J, Kang R and Tang D: Signaling pathways and defense mechanisms of ferroptosis. FEBS J. 289:7038–7050. 2022. View Article : Google Scholar : PubMed/NCBI | |
Cui J, Wang Y, Tian X, Miao Y, Ma L, Zhang C, Xu X, Wang J, Fang W and Zhang X: LPCAT3 is transcriptionally regulated by YAP/ZEB/EP300 and collaborates with ACSL4 and YAP to determine ferroptosis sensitivity. Antioxid Redox Signal. 39:491–511. 2023. View Article : Google Scholar : PubMed/NCBI | |
De Voeght A, Jaspers A, Beguin Y, Baron F and De Prijck B: Overview of the general management of acute leukemia for adults. Rev Med Liege. 76:470–475, (In French). PubMed/NCBI |