Genomic instability and clonal heterogeneity can influence cancer progression, response to therapy, and relapse. Chronic lymphocytic leukemia (CLL) harbors a variety of clones and subclones that will evolve differently according to intrinsic (microenvironment) and extrinsic (therapy) pressures. Different patterns of clonal evolution have been described, providing insights into the CLL leukemic cell, dynamics, selection, and treatment refractoriness. With the help of genomic technologies allowing a granular resolution of CLL clones, novel synergic therapeutic strategies can be tested with the aim of reaching a genomic–epigenomic ultrapersonalized, tailored approach. These efforts should consider the presence of targetable alterations, continuous cancer reshaping conferring disease refractoriness, and intratumoral clonal equilibrium to possibly avoid clonal selection.
Submitted January 2, 2020; accepted for publication July 15, 2020. Published online December 31, 2020.
Disclosures: The authors have disclosed that they have no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors.