E-Book

E-Book 3rd Congress

  • Ferroptosis: A Promising Therapeutic Target for Acute Leukemia
  • Roya Nekonam,1 Amirsoheil Karami,2,*
    1. Department of Microbiology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
    2. Department of Microbiology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran


  • Introduction: Acute leukemia, a type of blood cancer, manifests as an uncontrolled proliferation of abnormal white blood cells, disrupting the bone marrow and blood composition. Ferroptosis, a recently identified type of programmed cell death (PCD), has emerged as a promising therapeutic target for leukemia treatment. Ferroptosis is triggered by the excessive accumulation of reactive oxygen species (ROS) within cells. These highly reactive molecules can inflict damage on cellular components, disrupting normal cellular functions.
  • Methods: To gain a comprehensive understanding of the role of Ferroptosis in acute leukemia, a thorough literature search was conducted across PubMed, Google Scholar, and NCBI databases. This search identified 28 relevant articles that were carefully reviewed and analyzed to provide a deeper insight into this subject.
  • Results: The accumulation of reactive oxygen species (ROS) in leukemic cells is a hallmark feature that facilitates the induction of ferroptosis. This accumulation arises from a combination of factors, including: Impaired Glutathione Peroxidase 4 (GPX4) Activity: GPX4 is a crucial antioxidant enzyme that plays a pivotal role in detoxifying ROS. In leukemic cells, GPX4 activity is often compromised, leading to an inability to effectively neutralize ROS, rendering them more susceptible to ferroptosis. Increased ROS Production: Leukemia cells exhibit an abnormally high rate of ROS production, often stemming from mitochondrial dysfunction and other metabolic abnormalities. This enhanced ROS generation further contributes to the accumulation of ROS, amplifying the likelihood of ferroptosis. These molecular mechanisms underlie the susceptibility of leukemic cells to ferroptosis, opening up avenues for therapeutic intervention that target the regulation of ROS and the restoration of GPX4 activity. Several studies have demonstrated the efficacy of ferroptosis-inducing agents in inhibiting leukemia cell growth both in vitro and in vivo. These agents exert their effects by targeting the pathways that regulate ferroptosis. For instance, RSL3 is a small molecule that specifically targets the prolyl-4-hydroxylase (P4H) enzyme, disrupting its activity and leading to the accumulation of iron-sulfur clusters (ISCs) within cells. These ISCs interfere with the function of glutathione peroxidase 4 (GPX4). As a result, excessive ROS accumulate, triggering ferroptosis in leukemia cells. Ferroptosis-inducing gene therapy utilizes a gene therapy approach to deliver a proapoptotic protein, such as prolyl hydroxylase domain-containing protein 6 (PHD6), directly into leukemia cells. PHD6 promotes the degradation of GPX4, further impairing the cell's antioxidant defense and facilitating ferroptosis.
  • Conclusion: For all intents and purposes, ferroptosis emerges as a compelling therapeutic target for acute leukemia, with numerous studies validating the efficacy of ferroptosis-inducing agents in suppressing leukemia cell growth both in vitro and in vivo. Ongoing clinical trials are poised to further delineate the therapeutic potential of these agents in the treatment of acute leukemia, paving the way for novel and effective therapeutic strategies against this debilitating disease.
  • Keywords: Ferroptosis, Acute Luekemia, ROS, GPX4