Clin Pediatr Hematol Oncol.  2015 Apr;22(1):60-66. 10.15264/cpho.2015.22.1.60.

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

• Hahn SM
• Kwon SY
• Kim HS
• Han JW
• Lyu CJ

• KMID: 2168921
• DOI: http://doi.org/10.15264/cpho.2015.22.1.60

Abstract

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.

Keyword

DNA methylation; Pediatric acute lymphoblastic leukemia

MeSH Terms

Apoptosis
Biomarkers
Bone Marrow
Cell Cycle
Diagnosis
DNA Methylation*
Genes, Tumor Suppressor
Humans
Leukemia
Methylation
Precursor Cell Lymphoblastic Leukemia-Lymphoma*
Tissue Donors