Inhibition of Ezh2 preserves GVL effects. (A-B) Irradiated BALB/C recipients were transplanted with B6 TCD BM, with or without WT or T-KO T cells (1 × 106 CD4+ + 1 × 106 CD8+ T cells), and challenged with A20 cells (1 × 106/mouse). (A) The survival (pooled from at least 3 experiments) was monitored over time. ○, n = 11; ▪, n = 13; ▲, n = 19. P < .001, ○ versus ▲. (B) The graph shows the total body luminescence intensity. (C-D) Irradiated BALB/C recipients were transplanted with donor B6 TCD BM, with or without indicated doses of WT or T-KO T-KO cells and challenged with A20 cells (1 × 106/mouse) at the day of BMT. In one group, the recipient mice received T-KO (1 × 106) at days 0, 5, and 10 after transplantation, respectively. (C) The graph shows the total body luminescence intensity. (D) The survival was monitored. The death of GVHD or GVL was determined by necropsy. ○, n = 5; ▪, n = 5; □, n = 5; ▲, n = 5; △, n = 5; ▼, n = 5; ▽, n = 10. (Leukemia death: P < .05, ○ vs △, and ○ vs ▼; P < .01, ○ vs ▽. GVHD death: P < .001, ▪ vs ▲, ▪ vs △, ▪ vs ▼, ▪ vs ▽). (E-F) Lethally irradiated BALB/C recipients were transplanted with donor B6 TCD BM, with (▲, n = 10) or without (○, n = 7) T cells (0.2 × 106) isolated from hetero T-KO mice, and challenged with A20 cells. (E) The survival was monitored over time. P < .001, ○ vs ▲. (F) In vivo bioluminescence analysis of leukemia growth. Error bars indicate mean ± SD. *P < .05, ***P < .001.
