Distribution of kinase domain mutations in 53 patients
Mutation . | No. of patients . | Imatinib sensitivity . |
---|---|---|
M244V | 8 | Intermediate |
L248V | 1 | Intermediate |
G250E | 4 | Intermediate |
G251D | 1 | NA |
Q252H | 2 | Intermediate |
Y253F | 3 | Insensitive |
Y253H | 3 | Insensitive |
E255K | 4 | Insensitive |
L273M | 1 | NA |
E279Z | 1 | NA* |
E282G | 2 | NA |
E292V | 1 | NA |
T315I | 2 | Insensitive |
R328M | 1 | NA* |
M351T | 3 | Sensitive |
E352D | 1 | NA* |
E352G | 1 | NA |
E355G | 1 | Intermediate |
F359I | 2 | NA |
F359V | 4 | Intermediate |
L364I | 1 | Sensitive |
V379I | 2 | Intermediate |
F382L | 1 | NA |
L387M | 2 | Sensitive |
M388L | 1 | Sensitive |
H396P | 1 | Sensitive |
H396R | 2 | Intermediate |
S417Y | 1 | NA |
I418V | 1 | NA |
E450G | 1 | NA |
E453D | 1 | NA* |
E453K | 1 | NA |
E459G | 1 | NA |
D482V | 1 | NA* |
F486S | 3 | Intermediate |
Mutation . | No. of patients . | Imatinib sensitivity . |
---|---|---|
M244V | 8 | Intermediate |
L248V | 1 | Intermediate |
G250E | 4 | Intermediate |
G251D | 1 | NA |
Q252H | 2 | Intermediate |
Y253F | 3 | Insensitive |
Y253H | 3 | Insensitive |
E255K | 4 | Insensitive |
L273M | 1 | NA |
E279Z | 1 | NA* |
E282G | 2 | NA |
E292V | 1 | NA |
T315I | 2 | Insensitive |
R328M | 1 | NA* |
M351T | 3 | Sensitive |
E352D | 1 | NA* |
E352G | 1 | NA |
E355G | 1 | Intermediate |
F359I | 2 | NA |
F359V | 4 | Intermediate |
L364I | 1 | Sensitive |
V379I | 2 | Intermediate |
F382L | 1 | NA |
L387M | 2 | Sensitive |
M388L | 1 | Sensitive |
H396P | 1 | Sensitive |
H396R | 2 | Intermediate |
S417Y | 1 | NA |
I418V | 1 | NA |
E450G | 1 | NA |
E453D | 1 | NA* |
E453K | 1 | NA |
E459G | 1 | NA |
D482V | 1 | NA* |
F486S | 3 | Intermediate |
NA indicates mutation previously described, but in vitro imatinib sensitivity not determined; and NA*, mutation not previously described.
The number of patients sums to 66 (not 53) due to the presence of multiple mutations in some patients.
In vitro imatinib sensitivity according to proliferation assays of cells transfected with each BCR-ABL variant.24 As per our previous thresholds,2 “sensitive” is defined as an IC50 of 1000 nM or less imatinib, and “insensitive” as an IC50 of more than 3000 nM. The imatinib sensitivity data are from O'Hare et al,24 except L248V,25 E355G,26 L364I,27 M388L,25 and F486S.28