Aberrant DNA Methylation of CDH1, p16 and DAPK in Childhood Acute Lymphoblastic Leukemia

Background: Hypermethylation of tumor suppressor gene has been reported in various types of leukemia with potential involvement in the inactivation of regulatory cell cycle and apoptosis genes. Methods: To evaluate the methylation status at initial diagnosis and morphologic complete remission (CR) period in childhood acute lymphoblastic leukemia (ALL), we analyzed the methylation status of three key genes (CDH1, p16 and DAPK) in 43 childhood ALL patients and 7 healthy bone marrow (BM) donors. Results: CDH1 was methylated in 26 (60.4%) patients, p16 in two (4.6%) patients and DAPK in six (13.9%) patients at the time of diagnosis. Twenty nine (67.4%) patients had methylation of at least one gene. None of the healthy BM donors showed methylation of the above genes. Age was the only factor which showed significant association with the presence of DNA methylation (P=0.03). None of the other clinicopathological factors showed association with initial methylation status. At the time of morphologic CR, all patients who had aberrant DNA methylation at the time of diagnosis had no detectable residual methylation. Conclusion: Since hypermethylation was found in around two thirds of pretreatment ALL patients and none in healthy BM donor, we suggest hypermethylation of some important genes is a biologic marker of childhood ALL. We recommend that further studies with a large number of patients should be conducted.ope