P15 and P16 Promoters Methylation Status in APL Patients Treated by Arsenic Trioxide.

Inactivation of tumor suppressor genes P15 & P16 due to Hypermethylation has a critical role in progression of cancer. We analyzed the meltylation status of promoter region of these two genes and their correlation with patients survival in APL patients treated with ATO without chemotherapy and /or ATRA.

Patients treated by Arsenic Trioxide without ATRA or chemotherapy and 45 newly diagnosed and 5 relapsed were enrolled in our study. Whole blood DNA was extracted and modified by sodium bisulphite reaction. Then methylation status was studied by MS-PCR and gel electrophoresis. Also for newly diagnosed patients, early mortality, disease-free and overall survival compared between methylated or non-methylated groups.

Of 45 new cases, 31patients(69%) had methylated P15 but no patient had methylated P16. Eighty percent of relapsed patients had methylated P15 too, and no relapsed patient had methylated P16. DFS and OS correlated significantly with methylation status of P15 ( P=0.05 and 0.04) for patients who achieve to CR after treatment but it has no correlation with early motility during treatment course. Actually methyaltion of P15 improve chance of DFS and OS.

P15 but not P16 is frequently methylated in APL. Although in some studies, methyaltion of P15 negatively affected prognosis of APL patients treated by ATRA but it has no adverse effect when Arsenic Trioxide used in induction and cosolidation.

No relevant conflicts of interest to declare.