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Abstract: Mutations in the Bcr-Abl kinase domain may cause, or contribute to, resistance to tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia patients. Recommendations aimed to rationalize the use of BCR-ABL mutation testing in chronic myeloid leukemia have been compiled by a panel of experts appointed by the European LeukemiaNet (ELN) and European Treatment and Outcome Study and are here reported. Based on a critical review of the literature and, whenever necessary, on panelists' experience, key issues were identified and discussed concerning: (1) when to perform mutation analysis, (2) how to perform it, and (3) how to translate results into clinical practice. In chronic phase patients receiving imatinib first-line, mutation analysis is recommended only in case of failure or suboptimal response according to the ELN criteria. In imatinib-resistant patients receiving an alternative TKI, mutation analysis is recommended in case of hematologic or cytogenetic failure as provisionally defined by the ELN. The recommended methodology is direct sequencing, although it may be preceded by screening with other techniques, such as denaturing-high performance liquid chromatography. In all the cases outlined within this abstract, a positive result is an indication for therapeutic change. Some specific mutations weigh on TKI selection.

Article: BCR-ABL kinase domain mutation analysis in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors: recommendations from an expert panel on behalf of European LeukemiaNet. Simona Soverini, Andreas Hochhaus, Franck E. Nicolini, Franz Gruber, Thoralf Lange, Giuseppe Saglio, Fabrizio Pane, Martin C. Müller, Thomas Ernst, Gianantonio Rosti, Kimmo Porkka, Michele Baccarani, Nicholas C. P. Cross and Giovanni Martinelli.  Vorab online veröffentlicht am 11. Mai 2011,

Link to abstract:

Scientific Reference: doi:10.1182/blood-2010-12-326405, Blood 2011 118: 1208-1215, prepublished online 11 May 2011