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. 2014 May 8;124(6):2585–2598. doi: 10.1172/JCI73448

Figure 7. B-I09 suppresses leukemic growth and is well tolerated in mice.

Figure 7

(A) Pharmacokinetic analysis of B-I09 is described in Methods (n = 3; mean ± SEM). The terminal half-life (T1/2), time of peak concentration (Tmax), maximum concentration (Cmax), and AUC versus time calculated using zero to infinity (AUCinf) of B-I09 in mouse plasma are indicated. (B) CLL-bearing Eμ-TCL1 mice were intraperitoneally injected with DMSO (n = 3) or B-I09 (50 mg/kg in DMSO, n = 8) daily for the first 5 days of each of 3 weeks. Blood was collected to measure lymphocyte numbers using a HemaTrue Hematology Analyzer (HESKA). Data were compared with lymphocyte counts prior to B-I09 injections and plotted as mean ± SEM. (C) Lymphocyte counts in the peripheral blood of B-I09–treated Eμ-TCL1 mice (n = 8) were plotted as mean ± SEM. (D) PBMCs from B-I09 mice, before and after injections, were lysed for analysis of indicated proteins. (E) Splenocytes from DMSO- or B-I09–injected Eμ-TCL1 mice were stained with IgM-PE-Cy7, B220-FITC, CD5-APC, annexin V–PE, and 7-AAD. Gated IgM+B220+CD5+ splenic CLL cells were analyzed for annexin V– and/or 7-AAD–positive populations. (F) Percentages of apoptotic cells in gated IgM+B220+CD5+ CLL populations from spleens of DMSO-injected (n = 3) or B-I09–injected (n = 8) Eμ-TCL1 mice were plotted as mean ± SEM. (G) Weight of DMSO-injected (n = 3) or B-I09–injected (n = 8) Eμ-TCL1 mice was plotted as mean ± SD. (H) Paraffin-embedded sections of indicated organs from Eμ-TCL1 mice receiving 3 weeks of injections with DMSO or B-I09 were stained with H&E. Scale bars: 80 μm.