The HDACi LAQ824 and LBH589 induce cell death in Eμ-myc lymphomas both in vitro and in vivo. (A) Eμ-myc lymphoma cells were incubated for 24 hours with the indicated concentrations of LAQ824 or LBH589. Cell viability was determined by the uptake of PI and FACS analysis. (B) Whole cell lysates were prepared from Eμ-myc lymphoma cells that had been treated for 2 hours with vehicle, LAQ824 (25 nM), or LBH589 (4 nM). Western blot analysis was performed with antibodies specific for acetylated histone H3. Equivalent protein loading was confirmed by probing for β-actin. (C) Eμ-myc lymphomas were treated with LAQ824 (25 nM) or LBH589 (4 nM) for the indicated times, and apoptosis was assessed by flow cytometric analysis of Δψm, caspase activation, presence of cells with < 2n DNA content (sub G₁), and surface exposure of phosphotidylserine (annexin V staining). Each dose or time point represents the mean value of 3 individual experiments ± SE. (D) C57BL/6 mice bearing palpable Eμ-myc lymphoma cells were treated intravenously with LAQ824 (75 mg/kg) or LBH589 (80 mg/kg), and lymph nodes were harvested at the indicated times. Histologic sections were assessed by hematoxylin and eosin staining (top panel), immunohistochemistry using antibodies to acetyl histone H3 (middle panel), and TUNEL staining (bottom panel). Each time point is representative of an individual mouse. (E) C57BL/6 mice bearing an Eμ-myc lymphoma were treated with vehicle (200 μL 10% lactic acid/D5W; n = 10), LAQ824 (75 mg/kg; n = 10), or LBH589 (80 mg/kg; n = 10). Kaplan-Meier survival curves of mice treated with vehicle (black line), LAQ824 (blue line), or LBH589 (red line) are shown. (F) WBC counts of mice bearing an Eμ-myc lymphoma were taken 3 days after treatment with vehicle, LAQ824, or LBH589. Each point represents the mean value of 3 individual mice ± SE (*P = .01; #P = .004).