Epigenetic alterations ofp15INK4Bandp16INK4Agenes in pediatric primary myelodysplastic syndrome

We studied the methylation status of the p15INK4B and p16INK4A genes in 47 pediatric patients with primary MDS, its correlation with subtype, and the role of p15INK4B and p16INK4A in the evolution of MDS toward AML. Aberrant methylation of the p15INK4B gene was detected in 15 of 47 patients (32%), whereas only four patients demonstrated methylation of the p16INK4A gene (8%). The frequency of p15INK4B methylation was significantly higher in RAEB and RAEB-t subtypes (p < 0.003). Aberrant methylation of the p16INK4A gene was also more frequent in the subtypes that characterize advanced stages of the disease (p < 0.05). Evolution of disease was verified in 17 (36%) of the 47 patients. The association of p15INK4B and p16INK4A methylation status with evolution of disease was clearly significant (p < 0.008 and p < 0.05, respectively). These results suggest that methylation of the p15INK4B and p16INK4A genes is an epigenetic biomarker of pediatric disease evolution.