ALL-003: Value of Autophagy Related Gene 5 (ATG5) Expression as a Prognostic Marker in Adult Patients with Newly Diagnosed Acute Lymphoblastic Leukemia (ALL)

Abstract

Context: Autophagy is considered a pivotal cellular mechanism to cope with stress and maintain homeostasis. It is frequently dysregulated in different types of cancers with some exhibiting excessive and others having reduced autophagy levels. Objectives: To determine autophagy status in newly diagnosed adult acute lymphoblastic leukaemia (ALL) patients compared to age and sex matched controls. Moreover, its prognostic impact on disease characteristics and response to treatment was evaluated. Design: Prospective study. The patients were followed up to 12 months. Setting: Clinical Hematology and Oncology unit, Internal Medicine department, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Patients: Thirty-five newly diagnosed adult ALL patients were recruited and age and sex matched to 15 healthy control subjects. Intervention: ATG5 expression was measured on diagnosis using real-time quantitative polymerase chain reaction (qPCR). Cases have been followed up for one year after enrollment into the study. Main Outcome Measures:: To measure ATG5 in newly diagnosed ALL patients and correlate its level with clinical outcome and treatment response. Results: Mean ATG5 expression in ALL was twice that of controls which exhibits high statistically significant difference (2.15 + 2.2 vs 1.09 + 0.47, P value = 0.01). Its high expression has been significantly associated with B-ALL phenotype, lower haemoglobin and lower platelet counts. Of note, higher expressor group had higher bone marrow and peripheral blood blast percentages, more likelihood to develop chemoresistance to frontline agents; however, this did not show statistical significance. Further studies with the recruitment of larger sample of patients is needed to examine a relationship between autophagy activation and therapeutic outcome in ALL. Conclusion: Our study demonstrates that classic autophagic pathway may be activated in ALL patients and that it may be associated with more aggressive tumour behaviour and worse outcome.