CD44 deficiency mediates higher basal apoptosis and a milder presentation in murine CLL. (A) Charted are CD5⁺ B cells over time in the PB of Eµ-TCL1:CD44wt (black circles) and Eµ-TCL1:CD44ko (gray circles) mice. After 12 months, there is a significantly higher CD5⁺ B-cell count in the PB of leukemic Eµ-TCL1:CD44wt mice (n = 30; median, 24 496; range, 653-535 108) as compared with the Eµ-TCL1:CD44ko animals (n = 28; median, 9481; range, 37-228 769; P = .027). (B) In leukemic mice (age ≥ 12 months), spleen weights of Eµ-TCL1:CD44wt animals (n = 13; median, 2.1 g; range, 0.2-5.1 g) were significantly higher (P = .016) than in Eµ-TCL1:CD44ko animals (n = 16; median, 0.7 g; range, 0.2-2.6 g). (C-D) CD44 deficiency is associated with increased apoptotic CLL cell numbers in vivo as determined in murine splenic sections by immunohistochemistry for cleaved caspase-3 (left panels of C and D) and TUNEL staining (right panels of C and D). Mean ± SEM positive cells per 10 high-power fields per animal: cleaved caspase-3, Eµ-TCL1:CD44wt, 3.0 ± 0.3 vs Eµ-TCL1:CD44ko, 14.2 ± 0.9 (P < .0001); TUNEL, Eµ-TCL1:CD44wt, 6.2 ± 0.6 vs Eµ-TCL1:CD44ko 16.9 ± 1.1 (P < .0001). (E) Kaplan-Meier plots with log-rank statistics indicate a significantly prolonged leukemia-specific OS of those animals lacking CD44 expression. Median OS was 358 days for Eµ-TCL1:CD44wt mice vs 419 days for the Eµ-TCL1:CD44ko cohort. HPF, high-power fields.