RT Journal Article
SR Electronic
T1 Epigenetic dysregulation of the death-associated protein kinase/p14/HDM2/p53/Apaf-1 apoptosis pathway in multiple myeloma
JF Journal of Clinical Pathology
JO J Clin Pathol
FD BMJ Publishing Group Ltd and Association of Clinical Pathologists
SP 664
OP 669
DO 10.1136/jcp.2006.038331
VO 60
IS 6
A1 Chor-Sang Chim
A1 Raymond Liang
A1 Tsz-Kin Fung
A1 Chi-Lung Choi
A1 Yok-Lam Kwong
YR 2007
UL http://jcp.bmj.com/content/60/6/664.abstract
AB Aim: To study the role of gene promoter hypermethylation of the putative tumour suppressor genes involved in the death-associated protein (DAP) kinase/p14/HDM2/p53/Apaf-1 apoptosis pathway in multiple myeloma (MM). Method: DNAs from 55 primary MM marrow samples and myeloma cell lines were analysed for aberrant promoter methylation of DAP kinase, p14 and Apaf-1 genes by methylation-specific polymerase chain reaction (MSP). Result: In the methylated positive control, the sensitivity of M-MSP for DAP kinase was 1×10−3. Aberrant hypermethylation of DAP kinase was found in 29/55 (52.7%) primary MM samples, whereas hypermethylation of p14 or Apaf-1 was undetectable in any of the samples tested. 5-Azacytidine treatment of two myeloma cell lines, WL2 and HS-Sultan, led to de-methylation and re-expression of DAP kinase, thereby confirming gene silencing associated with promoter hypermethylation. Hypermethylation of DAP kinase did not correlate with age, sex, paraprotein subtype or Durie–Salmon stage, but negatively affected the overall survival. Conclusion: Of the putative tumour suppressor genes in the DAP kinase/p14/HDM2/p53/Apaf-1 apoptosis pathway, only DAP kinase is frequently methylated in MM, which is associated with gene silencing and might be of prognostic significance. p14 and Apaf-1 were not methylated in MM.