Nilotinib produces a limited set of Bcr-Abl kinase domain mutations. The position of identified mutations within the Bcr-Abl kinase domain is shown for imatinib mesylate (above) and nilotinib (below). Point mutations that were identified in imatinib mesylate–resistant clones were described previously and are shown for comparison.33 (A) Twenty-six exchanges affecting 21 different positions were identified in cell clones resistant to 1, 2, or 4 μM imatinib mesylate (above). With nilotinib at 150, 200, 300, or 400 nM, 9 exchanges at 7 positions were found (below). S349L was identified in conjunction with Q252H. *Q252H/S349L double mutant. (B) Resistance mutations identified using imatinib mesylate at 4 μM (above) compared with 400 nM nilotinib (below).
