P-loop mutations and novel therapeutic approaches for imatinib failures in chronic myeloid leukemia

Table 1 Sensitivity of Bcr-Abl kinase domain P-loop mutants to imatinib, nilotinib and dasatinib

		Ba/F3 cellular proliferation IC₅₀ value
		Imatinib (nM)	Nilotinib (nM)	Dasatinib (nM)
M244V	P-loop	2000	38	1.3
G250E	P-loop	1350	48	1.8
Q252H	P-loop	1325	70	3.4
Y253F	P-loop	3475	125	1.4
Y253H	P-loop	> 6400	450	1.3
E255K	P-loop	>5000	200	5.6
E255V	P-loop	> 6400	430	11

Imatinib: sensitive (≤ 1000 nM), intermediate (≤ 3000 nM), insensitive (> 3000 nM). Nilotinib: sensitive (≤ 150 nM), intermediate (= 150 nM to 450 nM), insensitive (> 2000 nM). Dasatinib: sensitive (≤ 5 nM), intermediate (≤ 5 nM to 11 nM), insensitive (> 11 nM). (adapted from Ref. 11).
Sensitive
Intermediate sensitivity
Insensitive

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