Distribution of point mutations in colonies resistant to imatinib and PD166326 compared with imatinib-resistant patients. Ba/F3 cell colonies that displayed a resistant phenotype to imatinib or PD166326 were analyzed for point mutations within the Bcr-Abl kinase domain, SH3 domain, SH3-SH2 connector, SH2 domain, and CD linker. (A) Distribution of affected positions according to functional domains of Abl. C-Helix and SH2 contact region mutations occurred in imatinib-resistant colonies exclusively. (B) The mutation pattern observed with imatinib, PD166326, and imatinib-resistant patients. With imatinib, 116 resistant colonies with mutant Bcr-Abl contained 117 point mutations, including one colony with 2 point mutations (Q252H and Y253F). In 39 mutant colonies resistant to PD166326, 39 single point mutations were identified. Relative frequencies are itemized according to positions within the Bcr-Abl kinase domain. An asterisk identifies mutations that have not been described so far. For comparison, Bcr-Abl kinase domain mutations reported in 167 patients with CML (chronic phase, accelerated phase, or blast crisis) or Ph⁺ ALL and primary (4 patients) or acquired imatinib resistance (163 patients) are shown. ^6,8-11,23-26