Kinetics of CLL Subclonal Architecture: Spontaneous Disease Progression or Treatment-Induced Selection?

Recent advances in whole genome assessment have highlighted the presence of marked intraclonal heterogeneity in chronic lymphocytic leukaemia (CLL). It has been suggested that this heterogeneity plays an important role in disease progression and that treatment may facilitate the outgrowth of CLL subclones with a high proliferative advantage. Recent years have also seen the development of a number of novel therapeutic approaches for CLL, including a range of targeted treatments as well as immunochemotherapy. Consequently, there is a need to assess the effects that various treatments have on the subclonal architecture of CLL during disease progression as any changes could potentially influence future clinical decisions. In this study a cohort of 133 CLL tumours was analysed for the mutational status of 6 genes recurrently mutated in CLL; ATM, TP53, SF3B1, MYD88, BIRC3, and NOTCH1; by deep targeted sequencing with an allele depth of 3000-5000 reads.