Molecular profiling in CLL

Chronic lymphocytic leukemia (CLL) has an extremely heterogeneous clinical course, with some patients requiring immediate therapy and others living without need for treatment for decades. There has been considerable interest in the underlying molecular mechanisms of this heterogeneity to understand not only the expected clinical course for individual patients but also the underlying pathogenesis of this disease. A number of clinical parameters have been identified that are predictive of the clinical course. More recently, a number of molecular biomarkers, most notably cytogenetics by fluorescent in situ hybridization (FISH), immunoglobulin heavy chain (IgVH) mutational status and expression of ZAP70, have been identified and verified as also providing prognostic information. The current challenge is to understand how we should use this new information in clinical practice and whether we should alter treatment based upon the detection of "high-risk" features. Over the past decade there has been considerable progress in development of more effective treatments for CLL, but current consensus is that treatment of CLL should be based upon the treatment of symptomatic disease. Specific treatment decisions based upon the detection of "high-risk" features remains a question for clinical trials, which will address the potential value of early treatment for specific groups of patients and whether all patients with CLL should receive a standard treatment or whether treatment should be modified in different risk groups.