Abstract:
:Mutations in the kinase domain (KD) of BCR-ABL are the most prevalent mechanism of acquired imatinib resistance in patients with chronic myeloid leukemia (CML). Here we examine predisposing factors underlying acquisition of KD mutations, evidence for acquisition of mutations before and during therapy, and whether the detection of a KD mutation universally implies resistance. We also provide a perspective on how the second-line Abl inhibitors dasatinib and nilotinib are faring in the treatment of imatinib-resistant CML, especially in relation to specific KD mutations. We discuss the growing importance of the multi-inhibitor-resistant 315T>I mutant and the therapeutic potential that a 315T>I inhibitor would have. Last, we assess the potential of Abl kinase inhibitor combinations to induce stable responses even in advanced CML and interpret the emerging data in the context of CML pathogenesis.
journal_name
Bloodjournal_title
Bloodauthors
O'Hare T,Eide CA,Deininger MWdoi
10.1182/blood-2007-03-066936subject
Has Abstractpub_date
2007-10-01 00:00:00pages
2242-9issue
7eissn
0006-4971issn
1528-0020pii
blood-2007-03-066936journal_volume
110pub_type
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