Relation of gene expression phenotype to immunoglobulin mutation genotype in B cell chronic lymphocytic leukemia. |
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| Authors: | A Rosenwald A A Alizadeh G Widhopf R Simon R E Davis X Yu L Yang O K Pickeral L Z Rassenti J Powell D Botstein J C Byrd M R Grever B D Cheson N Chiorazzi W H Wilson T J Kipps P O Brown L M Staudt |
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| Affiliation: | Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. |
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| Abstract: | The most common human leukemia is B cell chronic lymphocytic leukemia (CLL), a malignancy of mature B cells with a characteristic clinical presentation but a variable clinical course. The rearranged immunoglobulin (Ig) genes of CLL cells may be either germ-line in sequence or somatically mutated. Lack of Ig mutations defined a distinctly worse prognostic group of CLL patients raising the possibility that CLL comprises two distinct diseases. Using genomic-scale gene expression profiling, we show that CLL is characterized by a common gene expression "signature," 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. These genes were used to build a CLL subtype predictor that may help in the clinical classification of patients with this disease. |
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