Figure 7. Bcl-2 Inhibition and p53 Activation Reciprocally Overcome Resistance of AML Primary Samples Both In Vitro and in a PDX Mouse Model.
(A) Apoptosis and live cell numbers of p53WT primary AML samples after treatment with indicated concentrations of RG (μM) for 48 hr. PB, peripheral blood. BM, bone marrow.
(B) Apoptosis and live cell numbers of three ABT-resistant primary samples after treatment with indicated concentrations of ABT, RG, or the combination for 48 hr.
(C) Schematic outline of the PDX mouse model of drug resistance.
(D) Representative flow cytometry plot showing engraftment of human AML cells (hCD45+) in murine femur BM on day 0 as in (C).
(E) Percentage of hCD45+ leukemic cells in murine BM on day 0 as in (C). The percentage of hCD45+ cells was calculated as: % hCD45+ cells = the number of hCD45+ cells/the sum of hCD45+ and mCD45+ cells.
(F) Flow cytometry analysis of hCD45+ leukemic cells in femur BM on day 28 as shown in (C). Three mice from each group were sacrificed and examined.
(G, H) Percentage of hCD45+ cells in femur BM (G) and images of representative spleens from sacrificed mice (H) on day 28 as in (C).
(I) Kaplan-Meier survival curves of mice engrafted with resistant primary AML cells (n = 7 per group). Statistical significance was evaluated using the log-rank test. NS, not significant.
Data in panels A, B, E, and G represent the means of triplicate experiments. Error bars, mean ± SD.