Fig. 2: B-cell specific loss of Nedd9 is sufficient to reduce CLL burden in TCL1 mice.

A Schematic representation of novel genetic loci for B-cell specific Nedd9 knockout. B Confirmation of B-cell specific loss of Nedd9 protein upon Cd19-dependent Cre-recombination. Cd19⁺ and Cd19⁻ cells were sorted from PBMC of mice with indicated genotypes using mouse Cd19-specific magnetic beads and indicated protein lysates where blotted for Nedd9. C Flow cytometric analysis of different B-cell subsets in spleens of WT (n = 4), CD19Cre^tg/wtNedd9^fl/fl and Nedd9^−/− mice, p (B1a cells CD19Cre^tg/wtNedd9^fl/fl vs. WT) = 0.035714; p (marginal zone B-cells CD19Cre^tg/wtNedd9^fl/fl vs. WT) = 0.035714. D Kaplan–Meier curve representing the overall survival of B lineage-specific Nedd9 knockout (TC-N), and control cohort (TC) from birth to moribund. Median survival TC-N = 419 days (n = 12), TC = 346 days (n = 12), p = 0.0031. E Flow cytometric analysis of CD19⁺CD5⁺ CLL cells in the peripheral blood of mice with (TC-N) and without (TC) B lineage-specific Nedd9 loss at indicated time points (as ratio of CLL cells/B-cells). P (2 months) = 0.6355; p (4 months) = 0.0273; p (6 months) = 0.0001; p (8 months) = 0.0369; p (10 months) = 0.6016. F Flow cytometric analysis of CD19⁺CD5⁺ CLL cells in PBMC of TC and TC-N mice at indicated time points presenting CLL incidence (CLL cells in PBMC > 20%). P = 0.0039. G Flow cytometric analysis of CD19⁺CD5⁺ CLL cells in bone marrow samples of age-matched TC and TC-N mice. P (6 months) = 0.0.0050; p (10 months) = 0.4664. H Flow cytometric analysis of CD19⁺CD5⁺ CLL cells in spleens of age-matched TC and TC-N mice. P (6 months) = 0.0782; p (10 months) = 0.0513. I Spleen weight relative to body weight of age-matched TC and TC-N mice. P (6 months) > 0.9999; p (10 months) = 0.0845. J Representative pictures of spleens from ten months old wildtype, TC and TC-N mice. Ruler unit in mm/cm.