However, there is a lack of systematic analysis of p15 epigenetic modification such as methylation in MM from different studies that can provide more powerful estimation of an effect.
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.
p14/p16 and p15 gene expression was assessed by quantitative polymerase chain reaction in purified plasma cells (PC) from 52 patients with symptomatic multiple myeloma (MM) and seven with smoldering MM in order to clarify the impact of these genes on the proliferative activity of tumor cells and patients' outcome. p15 expression was lower in symptomatic MM than in smoldering SMM (-1.80 vs.1.51,p=0.026); similar results were observed for p14/p16.
Our results in studies with cell lines and primary MM support the fact that hypermethylation of p16 and p15 plays an important role in MM tumorigenesis.
Here, p15 is most often inactivated, at particularly high frequencies in the disorders lacking any p15/p16 deletions: 40-80% p15met in AML, MDS and multiple myeloma.