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 Printable version |
Management of imatinib mesylate-resistances induced by BCR-ABL mutations in chronic myelogenous leukemia |
Hématologie. Volume 13, Number 6, 457-64, Novembre-Décembre 2007, Revue
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 Résumé
Article gratuit
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Author(s) : Franck-Emmanuel Nicolini, Sophie Ducastelle, Sélim Corm |
Summary : Imatinib mesylate (IM) significantly modified the general principles applied to the treatment and the follow-up of chronic myelogenous leukemia (CML). The initial enthusiasm is currently tempered by the onset of primary (rare) or secondary (more frequent) resistances to this targeted therapy. Progressively, different resistance mechanisms have been identified and the most frequent one is the onset of mutations in the peptide sequence of the ABL kinase domain, responsible for variable resistance phenotypes (from total insensitivity to IM [e.g. T315I mutation] to the persistence of a partial sensitivity to IM [e.g. M244V mutation]). Some mutations can be associated to other resistance mechanisms, which remain sometimes unknown. Some BCR-ABL mutations are now considered as markers for disease progression as clonal evolution was. Second and third generation tyrosine kinase inhibitors are now available and represent for the majority of the cases, a suitable option in order to control IM-resistance induced by BCR-ABL mutations. However, physicians still must be careful as all tyrosine kinase inhibitors available to date do not eradicate CML, and the permanent detection of BCR-ABL+ residual cells might lead to the emergence of later resistances initiated in this compartment. Subsequently, rigorous and careful follow-up of these patients has to remain. |
Keywords : chronic myelogenous leukemia, imatinib, mutation, BCR-ABL |
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