In the present study, we found that treatment of PEL cells with the DNA demethylating agent 5-AZA reduced STAT3 phosphorylation and impaired PEL cell survival, suggesting that it may be promising against PEL patients, while the inhibition of EZH1/2 histone-methylating enzyme by DS-3201 (valemetostat) slightly affected either STAT3 activation or survival in PEL cells. This evidence concerns the gene EZH1 and primary effusion lymphoma.