However, despite sharing a common signature CLLs expressing mutated and unmutated IgVH genes differentially express more than 100 genes. Among these, over-expression of genes encoding zeta-chain-associated protein 70 (ZAP-70), lipoprotein lipase (LPL), BCL-7a, dystrophin and gravin are observed in the aggressive unmutated cases, while stable mutated cases over-express Wnt3, CTLA-4, NRIP1 nuclear receptor gene, ADAM29 and the transcription factor TCF7 [53]. These results suggest that indolent mutated and aggressive unmutated CLLs constitute two variants of the same disease. The reasons accounting for these striking differences in clinical outcomes of these two variants remain unsolved. .
