Fig. 6.
Fig. 6. Proliferation of CML primitive progenitors is suppressed in cells exposed to imatinib mesylate. / Cell division in the presence of imatinib mesylate was measured for CML and normal progenitors by analysis using the fluorescent tracking dye CFSE. (A) Immunomagnetically purified CD34+ cells were uniformly labeled with CFSE and sorted for a narrow band (40 channels) of fluorescence (upper panel). The labeled cells were also sorted for CD34 and CD38 expression to yield subsets of primitive (CD34+CD38dim) and committed (CD34+CD38+) progenitors. (B) After a 96-hour exposure to imatinib mesylate (0, 1, or 5 μM), cells were analyzed by FACS for CFSE fluorescence. Representative data are shown for CML and normal primitive progenitors. The calculated PI for each plot is indicated. (C) The percentage of cells in each generation, as determined by computer fitting of the data, is summarized for CML and normal primitive progenitors. Data are shown as the mean ± SEM results from 4 independent experiments (n = 3 for CML progenitors exposed to 5 μM imatinib mesylate). Data shown are for cells not exposed to imatinib mesylate (▪), cells exposed to 1 μM imatinib mesylate (░), and cells exposed to 5 μM imatinib mesylate (⊠). Significant changes in the percentage of cells in any generation in response to imatinib mesylate exposure are indicated (2 asterisks, P < .01; and 1 asterisk,P < 0.05). (D) The PI for CML (—▾—) and normal (- - ♦ - -) samples is shown as a function of the imatinib mesylate concentration. Data shown in the left panel are the mean PI ± SEM values for primitive progenitors (n = 4). The same data after normalization to the PI in the absence of imatinib mesylate are shown in the right panel. Significant changes in the PI in response to imatinib mesylate exposure are indicated (3 asterisks,P < .001; 2 asterisks, P < .01; and 1 asterisk,P < .05). Concentrations of imatinib mesylate at which CML results differed significantly from normal results are indicated with daggers below the curve (3 daggers, P < .001; 2 daggers, P < .01; and 1 dagger,P < 0.05).

Proliferation of CML primitive progenitors is suppressed in cells exposed to imatinib mesylate.

Cell division in the presence of imatinib mesylate was measured for CML and normal progenitors by analysis using the fluorescent tracking dye CFSE. (A) Immunomagnetically purified CD34+ cells were uniformly labeled with CFSE and sorted for a narrow band (40 channels) of fluorescence (upper panel). The labeled cells were also sorted for CD34 and CD38 expression to yield subsets of primitive (CD34+CD38dim) and committed (CD34+CD38+) progenitors. (B) After a 96-hour exposure to imatinib mesylate (0, 1, or 5 μM), cells were analyzed by FACS for CFSE fluorescence. Representative data are shown for CML and normal primitive progenitors. The calculated PI for each plot is indicated. (C) The percentage of cells in each generation, as determined by computer fitting of the data, is summarized for CML and normal primitive progenitors. Data are shown as the mean ± SEM results from 4 independent experiments (n = 3 for CML progenitors exposed to 5 μM imatinib mesylate). Data shown are for cells not exposed to imatinib mesylate (▪), cells exposed to 1 μM imatinib mesylate (░), and cells exposed to 5 μM imatinib mesylate (⊠). Significant changes in the percentage of cells in any generation in response to imatinib mesylate exposure are indicated (2 asterisks, P < .01; and 1 asterisk,P < 0.05). (D) The PI for CML (—▾—) and normal (- - ♦ - -) samples is shown as a function of the imatinib mesylate concentration. Data shown in the left panel are the mean PI ± SEM values for primitive progenitors (n = 4). The same data after normalization to the PI in the absence of imatinib mesylate are shown in the right panel. Significant changes in the PI in response to imatinib mesylate exposure are indicated (3 asterisks,P < .001; 2 asterisks, P < .01; and 1 asterisk,P < .05). Concentrations of imatinib mesylate at which CML results differed significantly from normal results are indicated with daggers below the curve (3 daggers, P < .001; 2 daggers, P < .01; and 1 dagger,P < 0.05).

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