From Iron Chelation to Overload as a Therapeutic Strategy to Induce Ferroptosis in Leukemic Cells

Grignano, Éric; Birsen, Rudy; Chapuis, Nicolas; Bouscary, Didier

doi:10.3389/fonc.2020.586530

Cited by 34 publications

(26 citation statements)

References 106 publications

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“…Iron chelators prevent the induction of ferroptosis, and deferoxamine (DFO) exerts anti-leukemic effects by blocking ROS elaboration and iron-dependent enzymes. Targeted peptides and antibodies against transferrin are also used to treat AML, and transferrin has been used to deliver anti-leukemic drugs ( Grignano et al, 2020 ). While APR-246 and ATPR (a novel all-trans retinoic acid derivative) can both induce ferroptosis of AML cells and become targets for AML therapy ( Du et al, 2020 ; Birsen et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Construction and Validation of a Novel Ferroptosis-Related Prognostic Model for Acute Myeloid Leukemia

et al. 2022

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Acute myeloid leukemia (AML) is a clonal malignant proliferative blood disorder with a poor prognosis. Ferroptosis, a novel form of programmed cell death, holds great promise for oncology treatment, and has been demonstrated to interfere with the development of various diseases. A range of genes are involved in regulating ferroptosis and can serve as markers of it. Nevertheless, the prognostic significance of these genes in AML remains poorly understood. Transcriptomic and clinical data for AML patients were acquired from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). Univariate Cox analysis was performed to identify ferroptosis-related genes with prognostic value, and the least absolute shrinkage and selection operator (LASSO) algorithm and stepwise multivariate Cox regression analysis were utilized to optimize gene selection from the TCGA cohort (132 samples) for model construction. Tumor samples from the GEO database (136 samples and 104 samples) were used as validation groups to estimate the predictive performance of the risk model. Finally, an eight-gene prognostic signature (including CHAC1, CISD1, DPP4, GPX4, AIFM2, SQLE, PGD, and ACSF2) was identified for the prediction of survival probability and was used to stratify AML patients into high- and low-risk groups. Survival analysis illustrated significantly prolonged overall survival and lower mortality in the low-risk group. The area under the receiver operating characteristic curve demonstrated good results for the training set (1-year: 0.846, 2-years: 0.826, and 3-years: 0.837), which verified the accuracy of the model for predicting patient survival. Independent prognostic analysis indicated that the model could be used as a prognostic factor (p ≤ 0.001). Functional enrichment analyses revealed underlying mechanisms and notable differences in the immune status of the two risk groups. In brief, we conducted and validated a novel ferroptosis-related prognostic model for outcome prediction and risk stratification in AML, with great potential to guide individualized treatment strategies in the future.

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Section: Discussionmentioning

confidence: 99%

Construction and Validation of a Novel Ferroptosis-Related Prognostic Model for Acute Myeloid Leukemia

et al. 2022

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“…Along this line, different therapeutic strategies resulting in LIP increase could easily saturate the (limited) antioxidant cancer cell defenses and trigger ferroptosis. Indeed, radiotherapy and drugs such as ferumoxytol (iron nanoparticles approved for the treatment of iron deficiency) or erastin (and its analogues) are currently under active investigation in early clinical trials as combination partners for standard regimens due to their capability of acting as ferroptosis inducers [ 150 ]. Furthermore, according to Mai T.T.…”

Section: Iron In Time As New Target For Oncotherapymentioning

confidence: 99%

Iron Metabolism in the Tumor Microenvironment—Implications for Anti-Cancer Immune Response

Sacco

Battaglia

Botta

et al. 2021

Cells

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New insights into the field of iron metabolism within the tumor microenvironment have been uncovered in recent years. Iron promotes the production of reactive oxygen species, which may either trigger ferroptosis cell death or contribute to malignant transformation. Once transformed, cancer cells divert tumor-infiltrating immune cells to satisfy their iron demand, thus affecting the tumor immunosurveillance. In this review, we highlight how the bioavailability of this metal shapes complex metabolic pathways within the tumor microenvironment and how this affects both tumor-associated macrophages and tumor-infiltrating lymphocytes functions. Furthermore, we discuss the potentials as well as the current clinical controversies surrounding the use of iron metabolism as a target for new anticancer treatments in two opposed conditions: (i) the “hot” tumors, which are usually enriched in immune cells infiltration and are extremely rich in iron availability within the microenvironment, and (ii) the “cold” tumors, which are often very poor in immune cells, mainly due to immune exclusion.

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“…Compared with other tumor cells, leukemia cells display higher transferrin expression and iron content, which causes the accumulation of ROS in leukemia cells more easily and ferroptosis occurs after cells undergo irreparable peroxidative damage. Thereby, promoting ferroptosis via further enhancing the iron content in leukemia cells seems to become a feasible strategy for leukemia treatment, which is also one of the hotspots in this field ( 95 – 97 ).…”

Section: Role Of Ferroptosis In Hematologic Malignancies Treatmentmentioning

confidence: 99%

Ferroptosis: Redox Imbalance and Hematological Tumorigenesis

et al. 2022

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Ferroptosis is a novel characterized form of cell death featured with iron-dependent lipid peroxidation, which is distinct from any known programmed cell death in the biological processes and morphological characteristics. Recent evidence points out that ferroptosis is correlated with numerous metabolic pathways, including iron homeostasis, lipid metabolism, and redox homeostasis, associating with the occurrence and treatment of hematological malignancies, such as multiple myeloma, leukemia, and lymphoma. Nowadays, utilizing ferroptosis as the target to prevent and treat hematological malignancies has become an active and challenging topic of research, and the regulatory network and physiological function of ferroptosis also need to be further elucidated. This review will summarize the recent progress in the molecular regulation of ferroptosis and the physiological roles and therapeutic potential of ferroptosis as the target in hematological malignancies.

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From Iron Chelation to Overload as a Therapeutic Strategy to Induce Ferroptosis in Leukemic Cells

Cited by 34 publications

References 106 publications

Construction and Validation of a Novel Ferroptosis-Related Prognostic Model for Acute Myeloid Leukemia

Construction and Validation of a Novel Ferroptosis-Related Prognostic Model for Acute Myeloid Leukemia

Iron Metabolism in the Tumor Microenvironment—Implications for Anti-Cancer Immune Response

Ferroptosis: Redox Imbalance and Hematological Tumorigenesis

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