Cell-cycle analysis of Eμ^CycD1CD19^CREBim^fl/flmice that developed MCL. (A) Spleens from mice treated with weekly SRBC alone (first column), SRBC and pristane (second column), or SRBC and irradiation (third column) all show absence of BIM expression (first row), high Ki-67 staining (second row), and scattered phosphorylated-retinoblastoma protein expression (third row). (B) Gene expression profiling was performed on spleens from Eμ^CycD1CD19^CREBim^fl/fl mice stimulated with SRBC alone (2, 5, and 6), SRBC with irradiation (1, 3, and 7), or SRBC with pristane (4) that developed MCL (n = 7) and compared with Eμ^CycD1CD19^CREBim^fl/fl mice stimulated with SRBC alone (8 and 9), SRBC with irradiation (12-14), or SRBC with pristane (10 and 11) that did not develop disease (n = 7). Shown are gene expression intensities (row normalized) of cell cycle–related genes that manifested statistically significant differential regulation. (C) Probability densities for gene set activity estimated by QuSAGE of MCL-bearing vs nondiseased Eμ^CycD1CD19^CREBim^fl/fl mouse spleens for genes downregulated in E2F1 overexpressing cells (top), genes upregulated in retinoblastoma protein–deficient cells (middle), and genes that comprise a human MCL signature (bottom).