Genetic mutations in chronic lymphocytic leukemia: impact on clinical treatment

Several recurrently deregulated pathways implicated in the development of chronic lymphocytic leukemia (CLL) have been described over the last decades. Knowledge of the CLL genetic heterogeneity led to the definition of molecular biomarkers informing about prognosis and treatment outcome. Areas covered: English literature published from January 2008 through December 2018 was searched in PubMed, Cochrane Central Register of Controlled Trials, and hematology meeting abstracts to obtain literature on clinical predictive factors for CLL. Peer-reviewed articles were selected based on the following concepts: CLL and genetic predictive factors (ATM, IGHV, NOTCH1, SF3B1, TP53). Additional references were selected by navigating relevant articles' reference lists. Of the 252 identified articles, 60 met the selection criteria. Expert opinion: Treatment options for CLL have increased significantly with the introduction of the BTK inhibitors, PI3K inhibitors, BCL2 inhibitors, and novel anti-CD20 monoclonal antibodies. In this scenario, predictive biomarkers can assist physicians in optimizing treatment tailoring. Furthermore, treatment-emergent mutations leading to drug resistance are discovered in the majority of patients treated with BTK inhibitors and BCL2 inhibitors, which could be switched to an alternative option.