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Using genomic-scale gene expression profiling, we show that CLL is characterized by a common gene expression \u201csignature,\u201d irrespective of Ig mutational status, suggesting that CLL cases share a common mechanism of transformation and\/or cell of origin. Nonetheless, the expression of hundreds of other genes correlated with the Ig mutational status, including many genes that are modulated in expression during mitogenic B cell receptor signaling. 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