A panel of epigenetically dysregulated Wnt signaling pathway genes for non-invasive diagnosis of pediatric acute lymphoblastic leukemia.

Abstract

BACKGROUND\nGenetic and epigenetic dysregulation of Wnt signaling pathway is widely linked up with abnormal proliferation and/or epithelial-to-mesenchymal transition, in different cancer cell types.\n\n\nOBJECTIVE\nIn the present research, we have tested whether promoter DNA methylation of a set of Wnt/non-Wnt genes such as [cadherin-2 (CDH2)], present in circulation , could serve as bone-marrow biopsy surrogate and help in diagnosing the status, sub-type or treatment outcome in pediatric acute lymphoblastic leukemia (ALL) patients.\n\n\nMETHODS\nPromoter DNA methylation was quantified in the bisulfite modified blood from the pediatric ALL patients (n= 86) in comparison with age-matched cancer-free subjects (n= 28), using real-time methylation specific PCR followed by rigorous statistical validations.\n\n\nRESULTS\nThe observed methylation index, sensitivity and specificity of selected molecular markers (viz., SALL1, WNT5α, LRP1b, CDH2) in patients liquid-biopsies was clinically significant showing high positive correlation in the pre-B ALL cases (p-value < 0.001). A substantial drop in promoter methylation signal of the follow-up/post-treatment patients was also noted (p-value < 0.001), which suggested an impending role of minimally invasive liquid-biopsy approach in the diagnosis and/or therapeutic monitoring of pediatric leukemia.\n\n\nCONCLUSIONS\nWhilst the reported metadata provides useful insight into the plausible involvement of epigenetic glitches in leukemogensis, our findings strengthen the remarkable functional consequences of dysregulated Wnt signaling genes in the hematological malignancies besides offering a novel panel of epigenetic marks.