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Plasma cells from 84 patients were harvested from the bone marrow and were isolated using the Plasmagel method. RNA was isolated and then was hybridized to an Affymetrix oligonucleotide array. After background subtraction and data normalization, statistical analysis was conducted by the supervised classification method. A total of 2,169 genes (approximately 65% of the human genome) was analyzed. One hundred genes (approximately 4%) demonstrated differential expression between the patient subgroups. Fifty-seven of these 100 genes (a 2-fold change or greater) were clustered into 3 groups on the basis of expression patterns in patients treated with thalidomide. Twenty-seven genes in the largest cluster showed a trend toward an association with overall survival, and 2 genes showed strong association with survival. There were only a few validated target genes in the gene profile. However, thalidomide is an immunomodulator that may be effective in multiple myeloma. 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