Effect of in vivo ACY738 treatment on euTCL1 B cells. (A) euTCL1 B cells were injected into SCID mice, which were then fed vehicle only or treated with oral ACY738 (n = 6 per group). Tumor burden was quantified in peripheral blood at the time points indicated. Data are representative of 2 independent experiments. (B) Total B cells were isolated from spleens of immunocompromised adoptive transfer CLL mice. Proliferative capacity was measured by Ki67 staining and flow cytometric analysis (n = 5 per group). (C) Isolated B cells were cultured with 1 μg/mL of lipopolysaccharide for 72 hours, and the percentage of apoptotic B cells was quantified by annexin V staining (n = 3 mice per group). (D) B cells were stimulated ex vivo with 10 μg/mL of anti-mouse immunoglobulin M, and phosphorylated Bruton tyrosine kinase (BTK; Y223) was analyzed by flow cytometry (vehicle-only group, n = 6 and ACY738-treated group, n = 5). Error bars correspond to standard errors of the mean. *P < .05, **P < .005.