Impact of BCR-ABL mutations on patients with chronic myeloid leukemia
Therapies that target BCR-ABL in chronic myeloid leukemia, including imatinib, dasatinib and nilotinib, have dramatically improved patient outcome. BCR-ABL mutations, however, contribute to treatment resistance by disrupting drug contact sites or causing conformational changes thus making contact si...
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| Main Authors: | , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
15 Jan 2011
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| In: |
Cell cycle
Year: 2011, Volume: 10, Issue: 2, Pages: 250-260 |
| ISSN: | 1551-4005 |
| DOI: | 10.4161/cc.10.2.14537 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.4161/cc.10.2.14537
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| Author Notes: | Andreas Hochhaus, Paul La Rosée, Martin C. Müller, Thomas Ernst, Nicholas C.P. Cross |
| Summary: | Therapies that target BCR-ABL in chronic myeloid leukemia, including imatinib, dasatinib and nilotinib, have dramatically improved patient outcome. BCR-ABL mutations, however, contribute to treatment resistance by disrupting drug contact sites or causing conformational changes thus making contact sites inaccessible. Clinical data indicate that developing BCR-ABL mutations during imatinib treatment is predictive for shorter progression-free survival, and that outcomes may depend on mutation type or location. In vitro, dasatinib and nilotinib inhibit most imatinib-resistant BCR-ABL mutations, except for T315I. In clinical studies, other mutations associated with treatment resistance include V299L, T315A, and F317I/L for dasatinib and Y253F/H, E255K/V, and F359C/V for nilotinib. Evaluating patients with clinical signs of resistance for BCR-ABL mutations is an important component of disease monitoring, potentially facilitating selection of subsequent therapy. First-line treatment with dasatinib or nilotinib instead of imatinib may reduce emergence of resistance but novel agents are needed to overcome the problematic T315I mutation. |
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| Item Description: | Gesehen am 12.09.2022 |
| Physical Description: | Online Resource |
| ISSN: | 1551-4005 |
| DOI: | 10.4161/cc.10.2.14537 |