A number of studies have recently demonstrated that super-enhancers, which are 
large cluster of enhancers typically marked by a high level of acetylation of 
histone H3 lysine 27 and mediator bindings, are frequently associated with genes 
that control and define cell identity during normal development. Super-enhancers 
are also often enriched at cancer genes in various malignancies. The 
identification of such enhancers would pinpoint critical factors that directly 
contribute to pathogenesis. In this study, we performed enhancer profiling using 
primary leukemia samples from adult T-cell leukemia/lymphoma (ATL), which is a 
genetically heterogeneous intractable cancer. Super-enhancers were enriched at 
genes involved in the T-cell activation pathway, including IL2RA/CD25, CD30, and 
FYN, in both ATL and normal mature T cells, which reflected the origin of the 
leukemic cells. Super-enhancers were found at several known cancer gene loci, 
including CCR4, PIK3R1, and TP73, in multiple ATL samples, but not in normal 
mature T cells, which implicated those genes in ATL pathogenesis. A 
small-molecule CDK7 inhibitor, THZ1, efficiently inhibited cell growth, induced 
apoptosis, and downregulated the expression of super-enhancer-associated genes 
in ATL cells. Furthermore, enhancer profiling combined with gene expression 
analysis identified a previously uncharacterized gene, TIAM2, that was 
associated with super-enhancers in all ATL samples, but not in normal T cells. 
Knockdown of TIAM2 induced apoptosis in ATL cell lines, whereas overexpression 
of this gene promoted cell growth. Our study provides a novel strategy for 
identifying critical cancer genes.