期刊
CLINICAL LYMPHOMA & MYELOMA
卷 7, 期 -, 页码 S113-S119出版社
CIG MEDIA GROUP, LP
DOI: 10.3816/CLM.2007.s.011
关键词
dasatinib; imatinib resistance; nilotinib
类别
Chronic myeloid leukemia (CML) is characterized by the presence of the Philadelphia chromosome, which is associated with a balanced translocation involving chromosomes 9 and 22 to produce a fusion gene (bcr-abl) that gives rise to a constitutively activated Abl tyrosine kinase. This kinase led to the discovery of several small-molecule inhibitors, imatinib being the first and most successful of these. Resistance to imatinib results in some patients from Abl kinase point mutations. Overcoming imatinib resistance represents one of the biggest challenges facing clinicians in the modern management of CML. In this review, we discuss the current understanding of CML pathophysiology and mechanisms of imatinib resistance and how advancing this knowledge has led to the design of novel therapies in the area of blastic phase CML and Philadelphia chromosome-positive acute lymphoblastic leukemia with previous imatinib failure.
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