Here, dasatinib efficacy was analyzed in patients recruited to phase 2/3 trials with chronic-phase chronic myeloid leukemia with or without BCR-ABL mutations after prior imatinib. High response rates were observed in patients with the majority of different BCR-ABL mutation types, including highly imatinib-resistant mutations in L248, Y253, E255, F359, and H396, in addition to other common mutations in G250 and M351 (Figure 4).

Mutations were identified in 60 (60%) of these patients (all with imatinib-resistant CML-AP). Despite the presence of imatinib-resistant BCR-ABL mutations and their association with poor prognosis, at 8 months' follow-up, 73% of patients with an imatinib-resistant BCR-ABL mutation had achieved MaHR following treatment with dasatinib.

CONTRADICTING EVIDENCE: In our study, we investigated the activity of bosutinib, dasatinib, imatinib, and nilotinib against a panel of 18 mutated forms of BCR/ABL associated with imatinib resistance in CML and Ph+ acute lymphoblastic leukemia patients. The results are listed in Figure 1 (Table 1 lists all the actual values for the relative concentration that inhibits 50%).

CONTRADICTING EVIDENCE: At 5 nM dasatinib mutations of L248, Q252, E255, V299, T315, and F317 were recovered (Table 1)….Spectrum and frequency of BCR-ABL kinase domain mutations recovered in the presence of imatinib mesylate, nilotinib, and dasatinib.