NOTCH1 and B-cell chronic lymphocytic leukemia: Two recent studies employing next-generation sequencing (either whole exome or whole genome) molecularly annotated nearly 1,000 CLL samples, identifying previously unrecognized putative driver mutations (for example, inZNF292,ZMYM3,ARID1A,PTPN11,RPS15, andIKZF3), including some in non-coding DNA (for example, the 3′ region ofNOTCH1 that leads to aberrant splicing and increased NOTCH1 activity, and an enhancer located on chromosome 9p13 that results in reduced expression of PAX5), and many subclonal mutations and documenting frequent clonal evolution, even in the absence of therapy3,4.