APRIL accelerates leukemic onset in TCL1-Tg mice. (A) Detection of peripheral blood leukemic B cells in 4-, 6-, and 8-month-old mice belonging to the 4 different genotypes. CD5⁺/B220^– CLL cells were discriminated on CD19⁺ gated B cells. (B) Bar graphs representing percent of CD5⁺CD19⁺ cells (top) or CD5⁺CD19⁺ absolute numbers (bottom). (C) Spleens from double-Tg mice show a grossly disturbed architecture with indistinguishable B- and T-cell areas, a hallmark of advanced disease stage. Representative consecutive spleen sections of 4-month-old mice with indicated genotypes (n = 3 per genotype) stained with hematoxylin and eosin, CD3, and B220. Magnification ×40. (D) Kaplan-Meier survival curve for the 4 different genotypes: WT, APRIL-Tg, TCL1-Tg, and double-Tg. Mean life span (days) is indicated on the TCL1-Tg and double-Tg survival curves. Log-rank test P = .0011 as significance level comparing TCL1-tg with double-Tg mice. (E) TCL1-Tg and double-Tg leukemic cells are characterized by the same B-cell receptor clonality peak patterns. RNA from sorted normal B cells (B220^high/CD5^–) and leukemic B cells (B220^dull/CD5⁺) was used to assess B-cell receptor clonality by analysis of CDR3-family VDJ genes. Spectra of individual mice age 4 and 8 months showing an oligoclonal arising leukemic population in both genotypes. ns, not significant. *P < .05; ***P < .005.