Role of BIRC5 Gene as a Prognostic Marker in Pediatric Acute Lymphoblastic Leukemia

Background and objectives: Acute lymphoblastic leukaemia (ALL) is the most common malignancy diagnosed in children. Survivin, a small inhibitor-of-apoptosis protein (IAP) encoded by the baculoviral inhibitor of apoptosis repeat-Containing 5 (BIRC5) gene, plays critical roles in malignancy by preventing apoptosis through blocking caspase activity. The aim of this study was to assess the prognostic role of BIRC5 gene in paediatric ALL. Subjects and methods: The present study was carried out on 42 children with the’ novo ALL who were followed up for two years and 10 apparently healthy children of matched age and sex (controls). Each child was subjected to complete history taking, clinical examination, laboratory investigations the form of CBC, Leishman-stained peripheral blood smears, Lactate dehydrogenase (LDH), Bone marrow (BM) aspiration and examination of Leishman-stained smears, Immunophenotyping on BM samples for routine panel of ALL determined by flow cytometer and quantitative determination of survivin gene expression by real time PCR on BM samples. Results: Patients with ALL had a significantly higher BIRC5 expression than did the control group (P=0.0004). There was a significant increase in survivin gene expression level in T-ALL when compared to common BALL and pre B-ALL (P=0.001). A significant positive correlation was found between survivin expression and LDH, uric acid and white blood cells (WBCs) (r=0.47, P=0.002; r=0.31, P=0.05, r=0.62, P=0.001), respectively. A significant higher survivin expression levels, LDH and WBCs was found in children with unfavorable outcome. 94.5% of ALL patients with high survivin expression had an unfavorable outcome while, in ALL children with low survivin expression, only 25% had an unfavorable outcome (P=0.001). Conclusion: BIRC5 gene expression was correlated with unfavorable outcome of childhood ALL. So, its measurement at diagnosis may detect a high risk ALL subgroup.