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Objective.To investigate the frequency of p16 and p15 gene methylation in multiple myeloma (MM),and its relationship with bone marrow cell apoptosis and clinical outcome.Methods.Twenty two patients with MM were studied to detect p16 and p15 gene methylation.Methylation specific polymerase chain reaction (MSP) was used to detect gene methylation,and terminal transferase mediated dUTP nick end labeling (TUNEL) was used to detect cell apoptosis.Results.p16 and /or p15 gene methylatoin was detected in 10 of 22 patients (45.4%).There were 3 patients with p16 gene methylation,9 patients with p15 gene methylation,and 2 patients with both genes methylation.The incidence of methylation of p15 gene was higher than that of p16 gene (P< 0.05).The patients with p16 and/or p15 gene methylation had a delayed cell apoptosis,poor response to chemotherapy,and a short overall survival (OS).Conclusion.The methylation of p16 and/or p15 gene plays a key role in MM apoptosis pathogenesis.The patients with both p16 and p15 gene methylation had a poor prognosis.