Journal
PHARMACOGENOMICS
Volume 13, Issue 11, Pages 1271-1284Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/PGS.12.103
Keywords
Bcr-Abl kinase domain mutations; chronic myeloid leukemia; dasatinib; imatinib; nilotinib; resistance
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Funding
- Novartis
- Bristol-Myers Squibb
- ARIAD
- Pfizer
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Over the last decade, the treatment of chronic myeloid leukemia has progressed tremendously. The first-generation tyrosine kinase inhibitor imatinib is now flanked by two second-generation molecules, dasatinib and nilotinib - and others are in advanced clinical development. One of the reasons for such intensive research on novel compounds is the problem of resistance, that is thought to be caused, in a proportion of cases, by point mutations in Bcr-Abl. In this article, the authors review how the biological and clinical relevance of Bcr-Abl mutations has evolved in parallel with the availability of more and more therapeutic options. The authors also discuss the practical relevance of Bcr-Abl mutation analysis and how this tool should best be integrated in the optimal clinical management of chronic myeloid leukemia patients.
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