Table 1

Properties of different point mutations

AMN107-resistant BCR-ABL mutantConcentration at recovery, nMNo. of coloniesPercentage of total*IC50 of AMN107, nMIC50 of imatinib mesylate, nM
Wild-type< 10450
K247N12511.1690≈850
L248V25011.16675≈10 000
Q252H12522.3240≈1 300
Y253C25089.30600≈10 000
Y253H50078.141300≈10 000
E255K25033.49200≈10 000
L273F12511.1651750
E282K25022.32150≈1 550
K285N25022.32≈500≈3 500
V289L12511.16251 000
E292K12511.1690≈1 500
N297T12511.1630650
T315I5001112.79≈8000≈10 000
H375P12511.16501 100
T406I12511.1680≈1 400
W430L12522.3290800
E431G12511.1635≈650
  • Six mutations, namely L248V, Q252H, Y253C, Y253H, E255K, and T315I, identified here from the screen, have previously been reported in patients with CML receiving imatinib mesylate, and are known to be associated with imatinib mesylate resistance. All double-mutant clones were recovered at 500 nM concentration.

  • — indicates no recovery.

  • * (no. of individual colonies/total no. of colonies obtained) × 100.