Epigenetic Alterations of DLL4 and Hes5 in Acute Lymphoblastic Leukemia (ALL)

Abstract

Acute lymphoblastic leukemia (ALL) is a hematologic condition with more than a quarter of pediatric cancers. Aberrant promoter methylation of Notch pathway genes causes the deactivation of TSGs. The pathway is also considered a crucial factor in the pathogenesis of ALL due to its active involvement in B and T cell development. Hypermethylation of Notch pathway genes has been reported previously. In this study, the promoter methylation frequency of genes DLL4 and Hes5 of the Notch pathway were studied using methylation-specific PCR in 30 pediatric ALL blood samples against 10 healthy controls. The objective of the study was to find the subtype-specific diagnostic biomarker for ALL. Hypermethylation frequency of DLL4 in pre-B ALL and T-ALL samples was found to be 84.21% and 100%, respectively. Whereas, Hes5 showed 100% mixed methylation in both diseased and control samples. The results predicted the possible epigenetic changes of Notch pathway and the possible role of DLL4 as a diagnostic biomarker of ALL.