A Gene Expression Signature of Benign Monoclonal Gammopathy Evident in Multiple Myeloma Is Linked to Good Prognosis.

Monoclonal gammopathy of undetermined significance (MGUS) can progress to multiple myeloma (MM), often through a phase of smoldering MM (SMM). We hypothesized that a molecular signature of MGUS may be detectable in a subset of patients with MM. Applying Significance Analysis of Microarrays, 52 genes, involved in important pathways related to cancer, were found to be differentially expressed between plasma cells from 22 healthy subjects, 24 strictly defined MGUS/SMM and 351 symptomatic MM (P < .001). Unsupervised hierarchical clustering of 351 MM and 44 cases of MGUS and 16 cases of MM with a MGUS history, created two major cluster branches, one containing 82% of the MGUS cases and 28% of the MM, termed MGUS-like MM (MGUS-L MM). Using the same clustering approach on an independent cohort of 213 MM revealed 27% were MGUS-L. The MGUS-L MM signature was associated with a higher prevalence of low-risk clinical and molecular features and superior survival (P < .01), despite a lower incidence of complete remission (P = .006). The MGUS-L signature was also seen in 15 of 20 patients surviving more than 10 years after autotransplant. These data reveal molecular switches associated with the development and progression of plasma cell dyscrasias.