p21 can not only act as a direct cell cycle inhibitor but can also supress transcription of other cell cycle control genes and promote apoptosis.59 EZH2 inhibition has been shown to increase p21 expression in acute myeloma leukaemia and gastric cancer60, 61 independent of p53 status and in melanoma where EZH2 was shown to be able to overcome p53-dependent senescence to promote the malignant phenotype.62 Our results support these studies and thus in myeloma inhibition of EZH2 might be used to treat patients with high-risk disease. Here, CDKN1A is linked to plasma cell myeloma.