In particular, V299L, T315A and F317L/V/I/C are resistant to dasatinib...Y253H, E255K/V and F359V/C/I are resistant to nilotinib, and V299L to bosutinib.

Treatment recommendations based on BCR-ABL1 mutation profile...The table below lists the BCR-ABL1 mutations that should not be treated with bosutinib, dasatinib or nilotinib in the second-line setting...Nilotinib…T315I, Y253H, E255K/V, or F359V/C/I or G250E

...- Minimum of 2 calendar years of nilotinib treatment with at least the last 12 months of nilotinib treatment prior to pre-screening at approved total daily dose of 600 mg BID or at a reduced dose of 400 mg QD if required from the perspective of tolerance for BCR-ABL positive CML in documented chronic phase at the time of diagnosis...

Patients with mutations that were less sensitive to nilotinib in vitro (IC(50) > 150 nM; Y253H, E255V/K, F359V/C) had less favorable responses, as 13%, 43%, and 9% of patients with each of these mutations, respectively, achieved MCyR; none achieved CCyR. The most common mutations associated with progression were the E255K/V, F359C/V, Y253H, and T315I mutations.

CONTRADICTING EVIDENCE:...which shows a model of AMN107 in complex with Abl kinase mutant M351T, and shows that the sensitivity of Bcr-Abl mutants to AMN107 segregates into four categories: high (IC50 ≤ 70 nmol/L: M244V, G250E, Q252H, F3llL, F317L, M351T, V379I, L387M, H396P, H396R), medium (IC50 ≤ 200 nmol/L: Y253F, E255K, F359V), low (IC50 ≤ 450 nmol/L: Y253H, E255V), and insensitive (IC50 > 2 μmol/L: T315I).