Over the past decade, next-generation sequencing (NGS) studies have led to the discovery of recurrently mutated genes in CLL, such as NOTCH1, SF3B1, BIRC3, XPO1, POT1, NFKBIE and EGR2, that are associated with poor clinical outcome [13–21]. This evidence concerns the gene NFKBIE and B-cell chronic lymphocytic leukemia.