In line with prior studies that profiled epigenomic features of a large CLL cohort and discrete normal B cell subtypes along the differentiation program8,19, this extensive chromatin rewiring at super-enhancers is mediated by specific transcription factors, as evidenced by enrichment of their motifs in activated super-enhancers, including NFAT, a deregulated gene with functional and therapeutic potential in CLL8, and TCFL2, a downstream target of the WNT pathway overexpressed in CLL20 (Fig. 1e, f; Supplementary Data 2, 3). Here, LZTR1 is linked to B-cell chronic lymphocytic leukemia.