E-Book

E-Book 3rd Congress

  • Navigating the Duality of Autophagy in Leukemia Therapy
  • Baran Safdari,1,* Zahra Norizadeh,2 Ghazal Mohammadi,3 Issa Layali,4
    1. Islamic Azad University, Tehran Medical Branch
    2. Islamic Azad University, Tehran Medical Branch
    3. Islamic Azad University, Tehran Medical Branch
    4. Islamic Azad University, Tehran Medical Branch


  • Introduction: Autophagy, a ubiquitous cellular process, has evolved to degrade and recycle damaged or malfunctioning cellular components. This remarkable pathway plays a pivotal role in various cellular processes, encompassing cell survival, stress resistance, and metabolic regulation. In the context of leukemia, autophagy exhibits a dualistic nature, exhibiting both tumor-suppressing and tumor-promoting effects, contributing to the complex and intricate dynamics of this malignancy. Regulation of Autophagy in Leukemia: The intricate regulation of autophagy in leukemia is a multifaceted phenomenon, influenced by a diverse array of factors, including oncogenes, tumor suppressor genes, and environmental conditions. For instance, the oncogene MYC has been shown to enhance autophagy activity, whereas the tumor suppressor gene PTEN exerts an inhibitory influence on autophagy. Additionally, environmental factors such as hypoxia and nutrient deprivation can modulate autophagy activity.
  • Methods: To fully comprehend the tumor-suppressive role of autophagy in leukemia, a comprehensive literature search was conducted across reputable databases, including PubMed, Google Scholar, and NCBI. The search yielded 31 pertinent articles that were painstakingly reviewed and analyzed to gain a thorough understanding of this subject.
  • Results: A. Tumor-Suppressive Role of Autophagy in Leukemia: Autophagy, the process of degrading damaged cell components, can inhibit the growth and spread of leukemia by eliminating faulty mitochondria and cells carrying mutated oncogenes. Mitochondria, the cell's energy generators, can become dysfunctional, leading to the release of harmful reactive oxygen species (ROS) that damage DNA and other cellular structures. Autophagy acts as a scavenger, removing these damaged mitochondria, thereby reducing ROS production and safeguarding the cell's integrity. Additionally, autophagy efficiently eliminates oncogene- expressing cells, which are the driving force behind uncontrolled cell growth and leukemia. By engulfing these oncogene-expressing cells in Autophagosomes and delivering them to lysosomes for breakdown, autophagy effectively curbs leukemia progression. B. Tumor-Promoting Role of Autophagy in Leukemia: Despite its tumor-suppressing properties, autophagy can also exert tumor-promoting effects in the context of leukemia. Autophagy can provide cancer cells with a survival advantage by replenishing their nutrient and energy reserves, a particularly crucial factor in the nutrient-deficient environment of the bone marrow, where leukemia cells predominantly reside. Furthermore, autophagy contributes to leukemia progression by facilitating cancer cell evasion from immune surveillance. Autophagy degrades damaged proteins and organelles that would otherwise serve as potential markers for immune recognition, rendering cancer cells less apparent to the immune system, thereby granting them a clandestine advantage in the face of therapeutic interventions. C. Targeting Autophagy in Leukemia Therapy: Leukemia therapy has gained interest in targeting autophagy due to its ability to both promote and suppress leukemia growth. Two primary approaches to targeting autophagy are employed: inhibition and induction. Inhibition of autophagy involves targeting autophagy-related proteins (ATGs). Rapamycin, for instance, inhibits mTOR, a critical regulator of autophagy. Conversely, induction of autophagy targets autophagy-stimulating factors (ASFs). Chloroquine, for example, induces autophagy by increasing the activity of Beclin-1, an ATG protein.
  • Conclusion: Autophagy's influence in leukemia is intricate and multifaceted. It can both impede and accelerate leukemia's development and advancement. The mechanisms regulating autophagy in leukemia are complex and involve various factors. Exploring autophagy as a therapeutic target in leukemia is a burgeoning area of research.
  • Keywords: Autophagy, Leukemia, tumorigenesis