The unique gene expression profile of myeloma has allowed the identification of multitudes of genes that could be involved in the pathogenesis of myeloma, and that might become potential therapeutic targets. Myeloma can be distinguished accurately from normal plasma cells based on gene expression profiling of 120 genes; however, it is indistinguishable from MGUS by this approach. Myeloma can be subdivided molecu-larly into four groups (MM1-MM4) by an unsuper-vised hierarchical clustering, with the MM4 group being the highly proliferative myeloma cell lines and the MM1 group consisting of MGUS and normal plasma cells. The main difference lies in the high expression of genes involved in cell cycling and DNA metabolism in the MM4 subgroup,70,71 and correlates with a high incidence of karyotypic abnormalities, increased ^-microglobulin, and increased creatinine, all of which are features of high-risk disease.
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