Frequency of BCR-ABL mutations detected in clinical specimens (n = 177). Mutations cluster in 4 distinct regions of the kinase domain. Mutations of the P-loop (amino acids 248-255, green) are most common, followed by mutations of T315 (red), which forms a hydrogen bond with imatinib. M351 (turquoise) interacts with the SH2 domain and participates in autoregulation of kinase activity. The fourth cluster (magenta) encompasses the A-loop (amino acids 379-398).