Study of Expression of Autophagy Related Gene 5 (ATG5) in Egyptian Patients Newly Diagnosed with Acute Lymphoblastic Leukemia (ALL)

Abstract

Abstract: BACKGROUND Autophagy is the cellular mechanism for homeostasis maintenance and survival under stressful conditions like hypoxia and nutrient deprivation. It has been extensively studied in various types of malignancies. However, the relationship between cancer and autophagy is still controversial. Researchers have been focusing on the exploitation of autophagy in the invention of new cancer therapeutics. Acute lymphoblastic leukemia is one type of malignancies with the highest resistant rates and worst prognosis. Knowing whether autophagy has a role in its initiation or progression would be of a great benefit. It would open the door to adding autophagy modulator drugs to conventional treatments in clinical trials to improve disease outcome. AIM To assess the basal level of autophagy in newly diagnosed ALL cases using ATG5 expression level, a key autophagy gene, and detect the relationship between the level of autophagy and prognosis. PATIENTS AND METHODS 35 newly diagnosed ALL patients and 15 healthy controls were included in the study. ATG5 RNA transcript level was measured by real time RT-PCR in all subjects using peripheral blood samples. Patients were followed up monthly for a year by Bone marrow aspiration and minimal residual disease using multiparameter color flowcytometry to detect resistance and early relapse. RESULTS ATG5 expression level was significantly higher in the ALL patients compared to the control group. Cases had approximately twice the mean expression value of the control (2.15±2.2 vs 1.09 ± 0.47). (P value = 0.01). The median value of the ATG 5 expression of the cases was used as a cut point to divide them into two groups of low and high expression. More B-ALL patients were in the high ATG5 group (83% vs 53%, P value=0.05). In addition, the high ATG5 group displayed a significantly lower haemoglobin level, platelet count, LDH level and CD 8 expression than the low ATG5 group (Mean Hb level of 7.7 g/dl vs 9.6 g/dl respectively, P value=0.04, Mean Platelet count of almost 55 x 109/L vs 105 x 109/L respectively, P value = 0.01, Mean LDH level of 455 vs 1260 U/L respectively, P value=0.02, CD8 + patients 0% vs 23% respectively, P value=0.05). Although ATG5 level was also more associated with a higher white blood cell count, the presence of extramedullary disease, a positive Philadelphia chromosome and post induction refractoriness, no statistical significance was found. ATG5 expression neither showed a significant relation with patients overall survival nor their disease free survival. CONCLUSION Basal autophagy level is high in ALL disease and associated with more aggressive disease characteristics. More researches are needed to detect its clear relationship with disease prognosis.