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Association details:
Evidence:
Evidence Level:
Resistant: C3 – Early Trials
New
Source:
Title:

Dasatinib induces significant hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in accelerated phase

Excerpt:
Mutations were identified in 60 (60%) of these patients (all with imatinib-resistant CML-AP). Among the 60 patients with mutations, 26 unique imatinib-resistant mutations were identified, of which G250E was the most common (n = 9) (Table 5).
DOI:
10.1182/blood-2006-09-046839
Evidence Level:
Resistant: C3 – Early Trials
New
Source:
Title:

BCR-ABL tyrosine kinase inhibitors in the treatment of Philadelphia chromosome positive chronic myeloid leukemia: A review

Excerpt:
The second-generation BCR-ABL TKIs nilotinib (Tasigna®) and dasatinib (Sprycel®), showed significant activity in clinical trials in patients intolerant or resistant to imatinib therapy, except in those patients with the T315I BCR-ABL mutation…. the complete eradication of CML in patients receiving imatinib was limited by the emergence of resistance mostly due to mutations in the ABL kinase domain and to a lesser extent by molecular residual disease after treatment.
DOI:
https://doi.org/10.1016/j.leukres.2010.04.016
Evidence Level:
Resistant: D – Preclinical
New
Title:

Activity of Bosutinib, Dasatinib, and Nilotinib Against 18 Imatinib-Resistant BCR/ABL Mutants

Excerpt:
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%).
DOI:
10.1200/JCO.2008.19.8853
Evidence Level:
Resistant: D – Preclinical
New
Title:

The two major imatinib resistance mutations E255K and T315I enhance the activity of BCR/ABL fusion kinase

Excerpt:
When expressed in COS7 cells, the BCR/ABL construct with either E255K or T315I exhibited not only the resistance to imatinib but also the increase in activity to induce autophosphorylation...These results raise a possibility that the major imatinib resistance mutations E255K and T315I may confer the growth advantage on leukemic cells to expand in the absence of selective pressure from imatinib treatment.
DOI:
10.1016/j.bbrc.2004.05.113