title: Methylation pattern of calcitonin (CALCA) gene in pediatric acute leukemia.
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.
authors.affiliation: Department of Clinical Pathology, Ain Shams University, Cairo, Egypt. eman.ismail_70@yahoo.com
authors.forename: Eman Abdel Rahman
authors.initials: EA
authors.lastname: Ismail
authors.forename: Mahira Ismail
authors.initials: MI
authors.lastname: El-Mogy
authors.forename: Deena Samir
authors.initials: DS
authors.lastname: Mohamed
authors.forename: Rania Ali Hassan
authors.initials: RA
authors.lastname: El-Farrash
mesh_terms: D000293:Adolescent; D014408:Biomarkers, Tumor / Q000235:genetics; D002116:Calcitonin / Q000235:genetics*; D015740:Calcitonin Gene-Related Peptide; D002648:Child; D002675:Child, Preschool; D020732:Cytogenetic Analysis; D019175:DNA Methylation; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D011379:Prognosis; D011498:Protein Precursors / Q000235:genetics*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C000606589:CALCA protein, human; D011498:Protein Precursors; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide