CLL biology and prognosis

Chronic lymphocytic leukemia (CLL) follows an extremely variable course with survival ranging from months to decades. Recently, there has been major progress in the identification of molecular and cellular markers that may predict the tendency for disease progression in CLL patients. In particular, the mutational profile of Ig genes and some cytogenetic abnormalities have been found to be important predictors of prognosis in CLL. However, this progress has raised new questions about the biology and prognosis of the disease, some of which are addressed here. Such questions include: 1) What is the role of the B-cell receptor (BCR) in CLL pathogenesis? 2) Is CLL one disease? 3) Is CLL an accumulative disease? 4) What is the normal counterpart of the CLL B lymphocyte? 5) Have the Rai and Binet staging systems become obsolete? 6) Which is the best surrogate for Ig mutational profiles?