Table 1.
Effect of IM treatment on Bcr-Abl kinase activity and downstream signaling pathways in CD34+ cells expressing low and high levels of Bcr-Abl: relative activity
IM, μM | MIG R1 |
BAlo |
BAhi |
||||||
---|---|---|---|---|---|---|---|---|---|
0.00 | 0.10 | 1.00 | 0.00 | 0.10 | 1.00 | 0.00 | 0.10 | 1.00 | |
P-Bcr-Abl, n = 4 | NE | NE | NE | 1.78 ± 1.06 | 0.46 ± 0.2 | 0.09 ± 0.08 | 5.67 ± 3.46 | 2.06 ± 1.04 | −0.39 ± 0.59 |
P-Akt, n = 3* | 0.24 ± 0.16 | 0.21 ± 0.07 | 0.31 ± 0.13 | 0.43 ± 0.18 | 0.32 ± 0.09 | 0.32 ± 0.22 | 0.94 ± 0.44 | 0.47 ± 0.23 | 0.15 ± 0.06 |
P-MAPK, n = 3† | 0.26 ± 0.11 | 0.18 ± 0.03 | 0.27 ± 0.07 | 1.14 ± 0.35 | 0.20 ± 0.09 | 0.27 ± 0.10 | 1.75 ± 0.49 | 0.50 ± 0.16 | 0.20 ± 0.05 |
P-STAT, n = 4† | 0.28 ± 0.04 | 0.37 ± 0.11 | 0.39 ± 0.12 | 1.66 ± 0.28 | 0.60 ± 0.32 | 0.42 ± 0.22 | 3.01 ± 1.62 | 0.80 ± 0.33 | 0.10 ± 0.03 |
Bcl-XL, n = 3 | 1.48 ± 0.41 | 1.57 ± 0.51 | 1.52 ± 0.28 | 1.93 ± 0.16 | 1.36 ± 0.54 | 1.81 ± 0.75 | 5.81 ± 2.56 | 3.63 ± 1.46 | 2.49 ± 0.96 |
Mcl-1, n = 2 | 0.5 ± 0.09 | 0.5 ± 0.03 | 0.71 ± 0.08 | 3.13 ± 0.18 | 1.37 ± 0.67 | 1.56 ± 0.34 | 7.33 ± 0.89 | 2.35 ± 0.29 | 0.91 ± 0.41 |
Western blotting was performed as described in “Patients, materials, and methods” and as shown in Figure 5. Results were normalized to levels of actin on the same blots. Differences related to Bcr-Abl expression levels and IM exposure were analyzed using 2-way ANOVA; values are mean ± SEM.
BAlo indicates Bcr/ABL low; BAhi, BCR/ABL high; IM, imatinib mesylate; and NE, not evaluable.
P < .05 for IM-treated versus untreated cells.
P= .051 for BAlo versus BAhi cells.