Clonal evolution and intraclonal dynamics in 2 CLL patients relapsing after fludarabine, cyclophosphamide, and rituximab therapy. Examples based on whole-exome sequencing data from our recent study (Ljungström et al).⁵  (A) In addition to the founding clone that harbors a RPS15 mutation, 2 subclones were observed before treatment initiation, one of which carried a frameshift deletion within MGA. At relapse, the MGA-deleted subclone disappeared, while a new subclone containing a TP53 mutation emerged. (B) A marked shift in subclonal populations was observed; while 2 subclones harboring the classical 2-bp NOTCH1 deletion and the recurrent p.K700E mutation in SF3B1 were eradicated after treatment, a new subclone emerged harboring a stop-gain NOTCH1 mutation and an EGR2 mutation.