A gene set signature for the risk of progression in IgM MGUS to Waldenström Macroglobulinemia by microarray of B cells and plasma cells

IgM monoclonal gammopathy of undetermined significance (IgM MGUS) is an early precursor stage of the rare lymphoma Waldenström Macroglobulinemia (WM). Although comparative gene expression studies on WM, IgM MGUS, and normal B cells identified several genes differently expressed, reliable predictors of progression from IgM MGUS to WM have not yet been identified. We performed a microarray study on CD19+ and CD138+ cells of WM vs. IgM MGUS vs. CTRLs to determine gene signatures for both cell populations. We demonstrated that hematopoietic antigens, cell-adhesion molecules, Wnt signaling, BCR signaling, calcium signaling, coagulation cascade, and pathways responsible for cell cycle and proliferation were significantly enriched for genes expressed in B cells of WM vs. IgM MGUS vs. CTRLs. Notably, we showed nine genes which displayed the same expression levels in both WM and IgM MGUS compared to CTRLs, suggesting their possible role in the risk of transformation in IgM MGUS to WM. We performed GEP of 36 patients with WM, 13 patients with IgM MGUS, and 7 healthy subjects (CTRLs) using Affymetrix Human Genome U133 plus 2.0 array with the Gene Chip platform. Our aims were to identify gene expression signatures which characterize the 3 groups, and to determine possible genes involved in the risk of progression of IgM MGUS to WM.