Ultrapersonalized Medicine Approach in CLL: Focus on Genomic Instability and Clonal Evolution
Posted: Wednesday, March 10, 2021
A comprehensive review of genomic instability and clonal evolution—and the role these factors may play in the progression of chronic lymphocytic leukemia (CLL)—was recently published in JNCCN–Journal of the National Comprehensive Cancer Network. Davide Rossi, MD, PhD, and Adalgisa Condoluci, MD, of the Oncology Institute of Southern Switzerland, Bellinzona, envision a new concept of ultrapersonalized medicine based on knowledge of the genomic-epigenomic structure of CLL. “A combination of different agents would target a wide range of subpopulations, allowing the ability to overcome potential resistance mechanisms,” the authors explained.
Some genetic alterations are prevalent at CLL diagnosis, including 13q14 deletion and trisomy 12; other genetic events are acquired during clonal evolution and occur in a more advanced phase of the disease, such as IGHV lack of mutation, 17p13 deletion, and NOTCH1 mutation. Because CLL harbors various clones and subclones that evolve differently according to intrinsic and extrinsic pressures, the tumor can reshape evolutionarily by either selecting or suppressing subclones to optimize cancer progression under adverse conditions.
According to the study authors, the future of CLL treatment may involve sequentially targeting the specific genetic or epigenetic lesions that confer an aggressive or resistant phenotype to a clone. This strategy may reduce the heterogeneity of the disease and prevent the loss of effectiveness of targeted treatments. “These efforts should consider the presence of targetable alterations, continuous cancer reshaping conferring disease refractoriness, and intratumoral clonal equilibrium to possibly avoid clonal selection,” they concluded.
Disclosure: The authors reported no conflicts of interest.
