Survival of total and quiescent CML cells in culture in the presence of drug combinations. Cells were cultured in SFM supplemented with growth factors. (A) Total viable cells (n = 4) after 6 days culture in the different treatment arms. Data are expressed as a percentage of the no drug control and data are represented as mean plus or minus SEM. (B) Total undivided CD34⁺ CFSE^max cells (n = 4) present after 6 days culture. In addition to P values shown, P = .023 and P = .005 for no drug control versus BMS-214662 + IM and BMS-214662 + dasatinib, respectively. Data are expressed as a percentage of the no drug control, and data are represented as mean plus or minus SEM. (C) Representative FACS dot plots showing the presence of a large quiescent CML stem/progenitor cell population (boxed region) in the IM and dasatinib arms, but not the BMS-214662-containing arms. The percentage value in the lower right corner of each plot represents the number of quiescent CML cells remaining at the end of the culture period expressed as a percentage of the starting CD34⁺ cell number. (D) Representative FACS histogram plot demonstrating the antiproliferative effect of dasatinib and IM compared with no drug control and BMS-214662. (E) Histogram highlighting the cell frequency for each cell division in each treatment arm. In the no drug control and BMS-214662 arms, there is a relative lack of cells in the early divisions (arrowhead ≤ 4 divisions) with increased numbers of cells in the later divisions ( arrow ≥ 6 divisions), compared with the TKI-containing arms, which tended to group together (bracket), with increased cells in the early divisions and fewer cells in later divisions. Data represent mean of 4 experiments.