North American ATLL features a high frequency of epigenetic mutations that are prognostic. (A) OS of North American ATLL patients with epigenetic mutations is worse than those without these mutations. (B) OS of North American ATLL patients with TP53 mutations shows a trend toward worse survival, but it is not statistically significant. (C) EP300 mutations are associated with reduced p300 levels, as well as total and acetylated p53 levels, in primary patient samples. (D) Gene set enrichment analysis revealed enrichment of the P53_DN.V1_UP signature in the 2 EP300-mutated samples (ATL21 and ATL18) compared with 2 EP300 WT samples (ATL29 and ATL30).