The downregulation of TRAIL in BCR-ABL1-positive cells is mediated by a preferentially expressed antigen of melanoma (PRAME)/enhancer of zeste homolog 2 (EZH2) repression mechanism, and the inhibition of either PRAME or EZH2 expression increases TRAIL levels and sensitivity to TRAIL and to imatinib [90]. The gene discussed is PRAME; the disease is melanoma.