The Role of Autophagy-Associated Genes in the Pathogenesis of Patients with Acute Lymphoblastic Leukemia

Background: Expanding the knowledge of the underlying molecular mechanisms in acute lymphoblastic leukemia (ALL) is of great importance to improving treatment outcomes. Autophagy, a critical and evolutionarily conserved pathway, plays an important role in maintaining cellular homeostasis under stressful conditions. This pathway consists of several sequential steps. The present study aimed to evaluate the expression levels of autophagy-related protein 3 (ATG3), autophagy-related protein 5 (ATG5), autophagy-related protein 7 (ATG7), autophagy-related protein 14 (ATG14), and urothelial cancer-associated 1 (UCA1) genes in B-ALL patients in order to better comprehend the autophagy pathway in B-ALL. Materials and Methods: This research is a case-control study. The bone marrow of 50 newly diagnosed patients with B-ALL (mean age = 12.3 years) and 15 healthy controls (mean age = 13.4 years) was evaluated by real-time PCR to analyze the expression of the aforementioned genes. Additionally, morphological, immunophenotypic, and molecular analyses were conducted to examine the phenotypes, genotypes, and percentage of lymphoblasts, respectively. Results: The findings revealed that B-ALL patients exhibited significantly higher expression of ATG3, ATG5, ATG7, and ATG14 genes compared to the healthy volunteers (P < 0.001). However, there was no significant difference in UCA1 levels between the two groups (P > 0.05). Interestingly, ATG3, ATG5, ATG7, ATG14, and UCA1 had similar mRNA expression levels in the patients with different types of chromosome abnormalities and immunophenotypes. Conclusion: Based on these results, the substantial increase in the expression of ATG3, ATG5, ATG7, and ATG14 genes suggests that the autophagy pathway is activated in B-ALL patients. This activation may contribute to tumor growth. Furthermore, the detection of autophagy gene expression could serve as a novel marker to monitor the response of B-ALL patients to treatment.