Figure 2.

ABT-737 rescues clinical features of AML mice. (A) Kaplan-Meier survival curves showing prolonged survival of AML mice who completed treatment with ABT-737 (n = 26, red line), mice who failed to complete treatment (n = 10, blue line), and untreated mice (n = 63, black line) plotted from date of birth (P < .0001). (B) White blood cell counts (WBC) (pretreatment vs posttreatment, P < .0001), neutrophil counts (pretreatment vs posttreatment, P < .05), lymphocytes (pretreatment vs posttreatment, P < .0001), and platelet counts (PLT) (pretreatment vs posttreatment, P < .0001) are shown (mean ± standard deviation, n = 30 mice in the pretreatment and posttreatment groups; n = 31 in the untreated group). There were no significant differences between untreated and pretreatment AML groups. (C) Percentage AML BM blasts pretreatment and posttreatment after day 33 from start of treatment (n = 6 mice). Giemsa stained BM smears showing decreased marrow blasts after treatment (shown in low power [LP × 50 magnification]) and hematoxylin and eosin stained liver sections with infiltration in the untreated mice and clearance in the treated mice postday 33. Representatives of 3 mice: (D) differential survival of mice transplanted each with 10⁷ spleen cells from AML untreated (black) or treated (red) mice into lethally irradiated FVB/N recipients (n = 5 in each group) (log-rank χ² = 9.496; P < .005). (E) Significant reduction in the Lin-/Sca-1⁺/c-Kit⁺ (LSK) population of untreated (n = 12) and treated (n = 8) (P < .01); untreated mice analyzed compared with WT FVB/N mice (P < .01); treated compared with WT mice (n = 6) (P ∼ .1). (F) ABT-737 targets myeloid progenitors. Dot plots showing numbers of day 7 colony-forming unit–granulocyte macrophage per 3 × 10⁴ cells plated per dish from BMs of diseased untreated and normal mice (P < .001); untreated compared with treated mice were statistically different (P < .01) (mean ± standard deviation of n = 4 mice analyzed postday 33). There was no statistical difference between the WT and post-ABT-737 treatment groups (P ∼ .3).