Recent Advances in the Molecular Biology of Chronic Lymphocytic Leukemia: How to Define Prognosis and Guide Treatment.

Simple Summary: The therapeutic landscape of Chronic Lymphocytic Leukemia (CLL) has dramatically changed in recent years, with a shift from chemoimmunotherapy towards many new targeted agents, such as Bruton Tyrosine Kinase inhibitors (BTKi) and anti-BCL-2. We now need an accurate re-definition of prognostic/predictive parameters to support clinicians in choosing the more appropriate option. This review explores recent advances in the molecular biology of chronic lymphocytic leukemia, with the aim of identifying the most important biomarkers to define prognosis and to guide first-line and second-line treatment. Chronic Lymphocytic Leukemia (CLL) is the most frequent type of leukemia in Western countries. In recent years, there have been important advances in the knowledge of molecular alterations that underlie the disease's pathogenesis. Very heterogeneous prognostic subgroups have been identified by the mutational status of immunoglobulin heavy variable genes (IGVH), FISH analysis and molecular evaluation of TP53 mutations. Next-generation sequencing (NGS) technologies have provided a deeper characterization of the genomic and epigenomic landscape of CLL. New therapeutic targets have led to a progressive reduction of traditional chemoimmunotherapy in favor of specific biological agents. Furthermore, in the latest clinical trials, the minimal residual disease (MRD) has emerged as a potent marker of outcome and a guide to treatment duration. This review focuses on recent insights into the understanding of CLL biology. We also consider the translation of these findings into the development of risk-adapted and targeted therapeutic approaches. [ABSTRACT FROM AUTHOR]