Using cDNA microarrays, this study examined a novel function of CD82 in CD34+/CD38− AML cells, and found that CD82 positively regulates the expression of EZH2 via inactivation of p38 MPAK signaling, resulting in hypermethylation of the promoter regions of tumor suppressor genes, such as PTEN and p16. This evidence concerns the gene MAPK14 and acute myeloid leukemia.