Exploring the intricacies between drivers of ferroptosis and hematological neoplasms
Exploring the intricacies between drivers of ferroptosis and hematological neoplasms
Maryam Shayanmanesh,1,*Nikoo Navidi,2Niloofar Jaafari,3
1. Student Research Committee, Iran University of Medical Sciences, Tehran, Iran 2. Student Research Committee, Iran University of Medical Sciences, Tehran, Iran 3. Student Research Committee, Iran University of Medical Sciences, Tehran, Iran
Introduction: Hematologic malignancies comprise a variety of heterogeneous myeloid and lymphoid malignant cells derived from the differentiation block of immortal hematopoietic cells. The majority of patients display avoidance to apoptosis and, ultimately, will face the outcome of chemotherapeutic resistance and recurrence. Ferroptosis induction has been identified as a promising way to cause tumor cell death and overcome treatment failure. The term “ferroptosis” refers to an iron-dependent oxidative form of programmed cell death with the accumulation of lipid hydroperoxides on cellular membranes. It is characterized by unique morphological features and is tightly correlated with various molecular and biological processes, such as iron, amino acid, and lipid metabolism. Cellular pathways can be impacted by ferroptosis either intrinsically or extrinsically. The depletion of glutathione peroxidase 4 triggers the endogenous pathway, while the exogenous pathway can be initiated through the inhibition of cystine uptake or the induction of iron transporters. Excess cytoplasmic Fe2+ promotes ROS and lipid peroxide formation. Various studies have demonstrated that ferroptosis inducers (FINs) are imposed to eradicate malignant cells. The aim of this literature was to summarize the core concept of ferroptosis and to investigate FINs, circular RNAs (circRNAs), long non-coding RNAs (lncRNAs), and their mechanisms of action.
Methods: Multiple searches were conducted on different databases, including PubMed, Scopus, and Google Scholar. Our literature searches focused on studies with terms of “Ferroptosis”, “Xc- cystine transporter”, “LncRNAs”, “CircRNAs”, and “Hematological malignancies”. The search was limited to the years between 2001 and 2023.
Results: Numerous natural compounds, small molecules, and nanoparticles inducing ferroptosis have been able to affect cellular pathways either intrinsically or extrinsically. Likewise, dysregulation of circRNAs and lncRNAs, the two types of noncoding RNAs, has been related to ferroptosis and lipid peroxidation. The downregulation of circZBTB46 and circ-0000745 genes is related to ferroptosis in AML, while the upregulation of circKDM4C and LINC00618 genes is associated with ferroptosis in ALL and AML, respectively. Ultimately, the overformation of ROS through relevant metabolic processes, which are highly reactive with cellular components, specifically membrane phospholipids, leads to the accumulation of lipid hydroperoxides and cell membrane disorganization.
Conclusion: Findings suggest that induction of ferroptosis is beneficial, but more studies are required to properly comprehend the underlying mechanisms and clinical utility. A deep recognition of the interactions between ferroptosis and hematological malignancies would contribute to the development of effective therapeutic strategies and combination therapies to overcome resistance.