Fatemeh Karimpour

Acute myeloid leukemia (AML) remains a formidable clinical challenge due to high relapse rates and therapeutic resistance. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, glutathione depletion, and Glutathione peroxidase 4 (GPX4) inactivation, has emerged as a promising strategy to overcome apoptosis evasion in AML. This review synthesizes recent advances in ferroptosis biology within AML, highlighting the unique metabolic vulnerabilities of leukemic cells, including dysregulated iron homeostasis, elevated reactive oxygen species (ROS), and cystine/glutamine dependencies, that create a “ferroptotic trap.” Despite promising preclinical outcomes, challenges such as biomarker validation, metabolic evasion, and nanoparticle delivery optimization persist. By addressing these hurdles, ferroptosis induction represents a transformative paradigm for next-generation AML therapeutics, offering novel avenues to eradicate resistant clones and rewire immunosuppressive niches. We explore cutting-edge pharmacological inducers (e.g., erastin, APR-246) and nanoparticle-based technologies (e.g., ferumoxytol, FAST nanoparticles) that enhance tumor selectivity and synergize with conventional therapies. Additionally, we dissect ferroptosis-related gene signatures prognostic of survival and immune microenvironment interactions, revealing their potential for risk stratification and immunotherapy integration.

Background: Targeted therapy with small molecule inhibitors (SMIs) has been considered a highly effective therapeutic strategy for chronic lymphocytic leukemia (CLL). However, there is little information on the detailed mechanisms and association of SMIs with immune evasion mechanisms. Objectives: This study examined the effects of signaling pathway inhibitors ibrutinib, idelalisib, duvelisib, and venetoclax on the expression of immune checkpoint ligands: Programmed death ligand 1 (PD-L1), galectin-9 (Gal-9), cluster of differentiation (CD)200, CD155, and herpes virus entry mediator (HVEM) in CLL leukemic cells. Methods: Leukemic cells were isolated from fifteen CLL patients using the magnetic activated cell sorting method, confirmed by flow cytometry, and then cultured and treated with different SMIs for 72 hours. The optimal doses of the applied SMIs for in-vitro treatment were determined by MTT assay. The mRNA expression was measured by real-time PCR assay using β-actin as a housekeeping gene. Results: The purity of isolated CLL leukemic cells was determined to be more than 97%, as confirmed by dual-color flow cytometry. Based on the IC50 results obtained from the MTT assay, the optimal doses of 5, 15.03, 1.07 μM, and 0.5 nM were determined for ibrutinib, idelalisib, duvelisib, and venetoclax, respectively. None of the SMI drugs showed changes in PD-L1 expression levels compared to the untreated group. Additionally, the level of Gal-9 mRNA expression was slightly decreased in all treated groups. The expression level of CD155 was downregulated only after treatment with venetoclax, and an upregulation was observed in the other treated groups. Finally, ibrutinib and idelalisib indicated a mild non-significant upregulation in HVEM gene expression. Conclusions: Altogether, the treatment of leukemic cells with different SMIs in this study indicated increased or decreased variations in the expression level of immune checkpoint inhibitory ligands in CLL. Therefore, these mechanisms should be considered for further treatment approaches, especially for combinational strategies.

Cervical cancer (CC), caused by human papillomavirus (HPV), is a leading cause of female malignancies worldwide. Therefore, understanding the underlying mechanisms of CC development and identifying novel therapeutic targets are significantly important. Cisplatin resistance is a significant challenge in the management of CC. Recent studies highlighted the critical role of long non-coding RNAs (lncRNAs) in modulation of cisplatin resistance. This comprehensive review aims to collect the current understanding roles of lncRNAs and their involvement in cisplatin resistance in CC by highlighting key processes of cancer progression, including apoptosis, proliferation, angiogenesis and epithelial-to-mesenchymal transition (EMT). We discussed the role of lncRNA in CC resistance to cisplatin through molecular pathways and examined gene expression changes. We also discussed treatment strategies and factors that reduce CC resistance to cisplatin by targeting them. Graphical Abstract

Colesteryl ester transfer protein (CETP) plays a key role in the metabolism of lipoproteins; therefore, polymorphisms of its gene can affect susceptibility to coronary artery disease (CAD) in diabetes mellitus. The aim of the present study was to investigate association between I405V polymorphism of CETP gene and risk of CAD in patients with type 2 diabetes mellitus. The current case-control study was conducted on 143 patients with type 2 diabetes and angiographically diagnosed CAD and 150 patients with type 2 diabetes and without CAD. Genotyping was performed through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The presence of CAD was defined as higher than 50% reduction in coronary artery diameter. The genotype frequencies of I405V polymorphism were II (27.3% vs. 23.2%), IV (61.5% vs. 67.5%), and VV (11.2% vs. 9.3%) in diabetic with CAD compared to diabetic without CAD (χ2 = 1.164) (P = 0.55). The I and V alleles were found at frequencies of 63.6% and 61.6% in the diabetic with CAD group and 36.4% and 38.4% in the diabetic without CAD group (χ2 = 0.263) (P = 0.60). No significant difference was observed between two groups in terms of genotype and allele frequency. Moreover, no significant association was observed between II, IV, and VV genotypes and lipid profiles in both groups. However, a significant difference was observed between genotype distributions of I405V polymorphism in men according to the severity of CAD. It is speculated that I405V polymorphism may be associated with the severity of coronary artery stenosis only in men with type 2 diabetes mellitus.