bcr-abl RNAi sensitizes cells expressing imatinib-resistant His396Pro-Bcr-Abl domain mutation to imatinib. (A) 32Dp210-wt (•), 32Dp210-Thr315Ile (▴), and 32Dp210-His396Pro (□) were analyzed using MTT assay to determine their sensitivity to imatinib. IC₅₀ values were 0.3 μM in 32Dp210-wt, 1.4 μM in 32Dp210-His396Pro, and 5.2 μM in 32Dp210-Thr315Ile. Values are means ± SD of triplicates. (B) Breakpoint-specific siRNA treatment (200 nM) leads to reestablishment of sensitivity to imatinib in 32Dp210-His396Pro. After treatment, 32Dp210-His396Pro (i) and 32Dp210-Thr315Ile (ii) were exposed to imatinib mesylate. Sensitivity was analyzed using the MTT assay. In 32Dp210-His396Pro Bcr-Abl, RNAi resulted in a distinct down-regulation of imatinib IC₅₀ values ranging from 1.2 μM in control cells treated with BAF8 (•) and 1.1 μM in EPC (□) reaching 0.3 μM in cells treated with BAF7 (▴). Despite this, the sensitivity of 32Dp210-Thr315Ile did not change after siRNA treatment (IC₅₀: 4.9 [BAF7], 5.2 [BAF8], 4.6 [EPC]). Values are means ± SD of triplicates.