Aberrant methylation of the death-associated protein kinase 1 (DAPK1) CpG island in chronic myeloid leukemia.
The death-associated protein kinase 1 (DAPK1) gene is a candidate tumor suppressor (TSG) and the abnormal methylation of DAPK1 gene has been found in many carcinomas. The epigenetic changes of TSGs are now recognized as a mechanism contributing to the development of chronic myeloid leukemia (CML). To clarify the role of DAPK1 in CML, we examined the methylation status of DAPK1 in 49 patients with CML using methylation-specific polymerase chain reaction. The aberrant methylation of the DAPK1 gene was found in 25 of 49 (51.0%) CML cases, not in all controls. No correlation was found between DAPK1 gene methylation and the age, hematologic parameters, chromosomal abnormalities, the types and levels of bcr/abl transcripts of CML patients. However, correlation could be observed between the sex and the status of DAPK1 methylation in CML patients (R = 0.374, P = 0.008). Furthermore, there was a significant correlation between DAPK1 methylation and the stages of CML (R = 0.354, P = 0.013). The CML patients in accelerated phase (AP) and blast crisis (BC) had higher frequency of DAPK1 methylation than those in chronic phase (CP) (75.0% vs. 34.5%) (chi(2) = 7.776, P = 0.005). In one patient, the status of DAPK1 methylation became positive on the transition from CP to AP and BC. These results suggested that DAPK1 promoter methylation might play a significant role in the progression of CML.
Qian
Jun
J
Department of Hematology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, PR China. qianjun0007@hotmail.com
Wang
Ya-Li
YL
Lin
Jiang
J
Yao
Dong-Ming
DM
Xu
Wen-Rong
WR
Wu
Chao-Yang
CY
D000328:Adult; D000368:Aged; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D001483:Base Sequence; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D017931:DNA Primers; D064550:Death-Associated Protein Kinases; D005260:Female; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012689:Sequence Homology, Nucleic Acid
D051017:Apoptosis Regulatory Proteins; D017931:DNA Primers; C579096:DAPK1 protein, human; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases