Molecular Profiling in CLL

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Hematology 2008

Molecular Profiling in CLL

G. Gribben1

Correspondence: G. Gribben, Professor of Experiment Cancer Medicine, St.

Bartholomew's Hospital, Barts and the London School of Medicine, University of

London, UK; Phone +44 20 7882 6052; Fax +44 20 7882 6126; e-mail:

john.gribben@... .

Abstract

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.