Par-4 decelerates accumulation of CLL-like cells in Par-4 × TCL1 mice. Par-4 transgenic mice were bred to the TCL1 leukemia model to produce Par-4 × TCL1 mice. (A) Par-4 × TCL1 mice were checked for expression of both transgenes by immunoblot using lysate made from purified splenic B cells. (B) Cohorts of TCL1 mice (n = 14) and Par-4 × TCL1 mice (n = 21) were bled monthly starting at 6 months, and disease was tracked by flow cytometry that quantified the absolute counts of CD45⁺CD19⁺CD5⁺ leukemic cells per microliter of peripheral blood (P = .0049). (C) Representative dot plots of peripheral blood flow from TCL1 and Par-4 × TCL1 animals at 10 months of age. (D) Overall survival data displayed in a Kaplan-Meier curve (n = 9 TCL1, n = 14 Par-4 × TCL1, P = .0072). (E) Par-4^flox/flox mice were bred to CD19-Cre mice to produce a B-cell–specific Par-4 knockout line, which was verified by immunoblot using lysate from purified splenic B cells. Par-4 knockout mice were then bred to TCL1 mice to produce triple-transgenic Par-4^flox/flox × CD19-CRE × TCL1 mice. Cohorts of triple-transgenic (n = 5) and Par-4^flox/flox × TCL1 (n = 6) mice were bled monthly starting at 8 months, and disease was tracked as above. (F) Absolute counts of CD45⁺CD19⁺CD5⁺ leukemic cells per microliter of blood at ages 8 to 10 months (P = .0153). (G) Representative dot plots of peripheral blood flow from Par-4^flox/flox × CD19-CRE × TCL1 and Par-4^flox/flox × TCL1 animals at 10 months of age. (H) Overall survival data displayed in a Kaplan-Meier curve (n = 5 Par-4^flox/flox × CD19-CRE × TCL1, n = 4 Par-4^flox/flox × TCL1, P = .01). Bars in graphs displaying absolute leukemia cell counts indicate the mean, with error bars representing the standard error of the mean. Results were analyzed in a mixed-effect model for absolute leukemia cell counts and a log-rank test for differences in median survival time. FITC, fluorescein isothiocyanate; PE, phycoerythrin; TG, transgenic.