Methylation pattern of calcitonin (CALCA) gene in pediatric acute leukemia

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.