Figure 7

Genetic makeup of aberrant BCL2⁺IL6⁺AID⁻ B-cells. (a) Heat map of differentially expressed genes in fractionated B220⁺ B-cell (blue, n=8) vs intact WT (whole tissue) samples (green, n=18) obtained from disease-bearing BCL2⁺IL6⁺AID⁻ mice. Significantly up- and downregulated genes (red and blue, respectively) were determined as described in the legend of Figure 3a, using FDR 0.01, and fold change >2 or <−2. (b) Genetic pathway enrichment in B220⁺ cells identified by IPA. Online pathway repositories employed were as follow: K, KEGG W, Wikipathways; R, Reactome. Full designations of pathways 8 and 9 are IgSF family member proteins and systemic lupus erythematosus, respectively. (c) Representative metaphase spread of a tumor cell labeled with FISH probes annealing to the cellular oncogene, Myc, which resides on Chr 15 (red), or the Ig heavy-chain locus, Igh, on Chr 12 (green). Genetic recombination of Myc and Igh, which takes the form of a reciprocal chromosomal T(12;15) translocation, is a common feature of plasma cell tumors in C mice, providing the rationale for this analysis. (d) Bar graph diagram depicting genetic pathway similarity scores of mouse B-cells to human multiple myeloma (MM), chronic lymphocytic leukemia (CLL) and WM. The latter is represented by two different fractions: B cells (BC) and plasma cells (PC).