Prognostic and therapeutic implications of iron-related cell death pathways in acute myeloid leukemia.

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Iron homeostasis and cell death pathways play crucial roles in cancer pathogenesis, including AML. The objective of this study was to examine the clinical significance of genes involved in iron-related cell death and apoptotic pathways in AML, with the intention of providing insights that could have prognostic implications and facilitate the development of targeted therapeutic interventions. Gene expression profiles, clinical information, and molecular alterations were integrated from multiple datasets, including TCGA-LAML and GSE71014. Our analysis identified specific molecular subtypes of acute myeloid leukemia (AML) displaying varying outcomes, patterns of immune cell infiltration, and profiles of drug sensitivity for targeted therapies based on the expression of genes involved in iron-related apoptotic and cell death pathways. We further developed a risk model based on four genes, which demonstrated promising prognostic value in both the training and validation cohorts, indicating the potential of this model for clinical decision-making and risk stratification in AML. Subsequently, Western blot analysis showed that the expression levels of C-Myc and CyclinD1 were significantly reduced after CD4 expression levels were knocked down. The findings underscore the potential of iron-related cell death pathways as prognostic biomarkers and therapeutic targets in AML, paving the way for further research aimed at understanding the molecular mechanisms underlying the correlation between iron balance, apoptosis regulation, and immune modulation in the bone marrow microenvironment.", "claims": [{"id": "claim-method", "statement": "Ultimately, the Kaplan-Meier survival analysis was conducted to evaluate the prognostic implications of the 268 dysregulated genes associated with iron-mediated cell death or apoptosis, identifying 69 prognosis-related key genes (p<0.05), consisting of 11 iron death genes and 58 apoptosis genes.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37736548", "locator": "sections[4] \"Determination and analysis of ferroptosis and apoptosis protein-coding genes in AML\" paragraph 2", "quote": "Ultimately, the Kaplan-Meier survival analysis was conducted to evaluate the prognostic implications of the 268 dysregulated genes associated with iron-mediated cell death or apoptosis, identifying 69 prognosis-related key genes (p<0.05), consisting of 11 iron death genes and 58 apoptosis genes."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/ Supplementary Material . 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Subsequently, Western blot analysis showed that the expression levels o"], "order_basis": "paper_text_order:1287", "id": "assay:1"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["rlying the correlation between iron balance, apoptosis regulation, and immune modulation in the bon", "etermination and analysis of ferroptosis and apoptosis protein-coding genes in AML First, the limma", "nes were intersected with 660 iron death and apoptosis gene sets, resulting in 268 differentially e", "n 268 differentially expressed iron death or apoptosis genes. 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