The Other Evolves from More Differentiated B Cells

(memory B-cells) with somatically mutated heavy chain genes and has a good prognosis.10-12 However, recent data derived from gene expression profiling analysis failed to clearly distinguish unmutated and mutated cases and favor the view that all cases of CLL have a common cell origin and/or a common mechanism of malignant transformation.13,14 A recent study from our group on 18 cases of CLL, compared 9 Binet stage A cases with stable disease (i.e. at least 5 years without treatment and any evolution) and mutated Ig genes to 9 cases with stage B or C aggressive disease and unmutated Ig genes. In agreement with previous reports indicating that Ig mutated and unmutated cases have globally the same gene expression pattern, a supervised statistical analysis showed that only 85 genes were differently expressed by a factor >2 between the two groups of CLL. However, in contrast to previous reports, a non supervised hierarchical clustering analysis could clearly separate the stable mutated group from the aggressive unmutated one, except for one case (Davi et al., ASH meeting 2002). These results show that gene expression profiling can distinguish CLL cases with a stable evolution and mutated Ig genes from those with unmutated Ig genes and progressive disease. Thus, monitoring the expression of a very limited number of genes might suffice to identify patients displaying an indolent disease from patients exhibiting an aggressive one. Guillaume Dighiero Institut Pasteur, Paris