Splenocytes recovered from diseased Bfl-1ΔC/p53DD mice are tumorigenic and display up-regulation of Lck and RANK signaling pathway. (A) Kaplan-Meier curves show accelerated tumorigenesis in nude mice transplanted with splenocytes derived from 3 independent Bfl-1ΔC/p53DD mice (GFP-Bfl-1ΔC/p53DD vs tumor derived 1, P = .001; GFP-Bfl-1ΔC/p53DD vs tumor-derived 2, P = .001; GFP-Bfl-1ΔC/p53DD vs tumor derived 3, P = .001). Uninjected mice and mice injected with FL5.12 cells expressing p53DD alone, GFP-Bfl-1/p53DD, or parental FL5.12 cells expressing Bfl-1ΔC/p53DD served as controls. The arrowhead denotes a mouse that died of unknown cause. (B) Hierarchical clustering of genes up- or down-regulated 2-fold or greater in microarrays from 3 independent GFP-Bfl-1ΔC/p53DD tumors analyzed in duplicate experiments with the use of 2 different cell lines isolated from each tumor (eg, T1 vs T1A) versus parental FL5.12 cells expressing GFP-Bfl-1ΔC/p53DD. Data were normalized with the use of GeneSpring 7.2 analysis software. (C) Venn diagram representing genes up-regulated by 2-fold or greater in GFP-Bfl-1ΔC/p53DD tumors. (D) Selected genes commonly up-regulated in 3 independent GFP-Bfl-1ΔC/p53DD tumors versus parental cells. (E) Box plots showing significant up-regulation of Lck mRNA in primary specimens from human diffuse large B-cell lymphoma (DLBCL) and B-cell chronic lymphocytic leukemia (B-CLL) compared with normal B cells (Rosenwald dataset), as extracted from the Oncomine database.