Biomarkers in chronic lymphocytic leukemia: Clinical applications and prognostic markers

Chronic lymphocytic leukemia (CLL) is a heterogeneous disease with a variable clinical course. The Rai and Binet staging systems are often used to predict survival. However, they do not take into account other biological characteristics of CLL cells that may influence the disease course and response to treatment. Prognostic factors such as chromosome abnormalities (trisomy 12, 11q deletions and 17p deletions), β2 microglobulin, thymidine kinase, CD38 and ZAP-70 expression, IGHV mutation status, and mutations in genes such as NOTCH1, MYD88, SF3B1, and ATM are also predictors of prognosis. These biological markers have enabled the development of multiparameter risk models to predict overall survival. In addition, these models are useful for treatment decisions, as they can identify patients that could be treated with clinical trials vs. standard of care therapies. This chapter will review the most important prognostic markers that have been described in CLL and their application in clinical practice.