Abstract

Disruption of deoxyribonucleic acid (DNA) methylation patterns has emerged as one of the possible origins of leukemogenesis. Calcitonin (CALCA) gene is a hot-spot for gene hypermethylation in acute leukemias. This study aimed to systematically analyze the methylation status of CALCA gene in pediatric acute leukemia using methylation-specific polymerase chain reaction (MSP) and assess its value as a potential prognostic biomarker. The study population consisted of 70 children divided into; 35 acute myeloblastic leukemia (AML) and 35 acute lymphoblastic leukemia (ALL) patients. CALCA gene was found to be hypermethylated in 54.3% of AML and 65.7% of ALL patients. CALCA hypermethylation was neither correlated to any of the clinicopathologic characteristics of patients, standard prognostic factors nor response to induction therapy (P>0.05). Hypermethylated AML and ALL patients displayed poorer clinical outcome when compared with hypomethylated counterparts as evidenced by high relapse and mortality rates with the occurrence of early relapse (P<0.05). The estimated overall and disease-free survival rates at 2.5-years were significantly shorter for hypermethylated patients in both groups (P<0.01). Our results suggest that CALCA gene methylation pattern is an independent prognostic factor in pediatric acute leukemia that could characterize a group of patients with enhanced risk of relapse and death.