Figure 2. Cellular Derivation of Prognostic Gene-Expression Signatures in Diffuse Large-B-Cell Lymphoma.

Panel A shows the relative gene expression of the stromal-1, stromal-2, and germinal-center B-cell signatures in CD19+ malignant and CD19− nonmalignant subpopulations of cells isolated from three biopsy specimens from patients with diffuse large-B-cell lymphoma (DLBCL). Stromal-1 and stromal-2 signature genes were more highly expressed in the nonmalignant cells, whereas the germinal-center B-cell signature genes were more highly expressed in the malignant cells. The log₂ ratios of gene-expression levels in the CD19− subpopulation to those in the CD19+ subpopulation are depicted according to the color scale shown. Panel B shows the relationship of the stromal-1 signature to gene-expression signatures derived from normal cells. Gene-set enrichment analysis established a relationship between two signatures that are expressed in cells and tissues of mesenchymal origin (normal mesenchyme-1 and mesenchyme-2 signatures) and a monocyte signature, which is expressed more highly in normal blood monocytes than in B cells, T cells, and natural killer cells. No relationship was observed between the stromal-1 signature and a pan–T-cell signature, which is expressed more highly in T cells than in B cells, natural killer cells, and monocytes. The relative levels of gene expression within each sample are depicted according to the color scale shown. R-CHOP denotes rituximab plus combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone.