BACKGROUND: Although the vast majority of patients with chronic myeloid leukemia (CML) respond to the tyrosine kinase inhibitor (TKI) imatinib mesylate, resistance might occur de novo or during treatment. METHODS: The authors reviewed the known mechanisms of primary and secondary resistance to imatinib and other TKIs used in the management of CML. RESULTS: Mutations within the kinase domain of BCR-ABLI account for 30% to 40% of cases of imatinib resistance. Other mechanisms include BCR-ABLI amplification, overexpression of the SRC family of kinases, and pharmacokinetic and pharmacodynamic factors. CONCLUSIONS: Although not all resistance mechanisms have been identified and understood, several agents based on the known mechanisms have already been designed and developed and are beginning clinical trials.
BACKGROUND: Although the vast majority of patients with chronic myeloid leukemia (CML) respond to the tyrosine kinase inhibitor (TKI) imatinib mesylate, resistance might occur de novo or during treatment. METHODS: The authors reviewed the known mechanisms of primary and secondary resistance to imatinib and other TKIs used in the management of CML. RESULTS: Mutations within the kinase domain of BCR-ABLI account for 30% to 40% of cases of imatinib resistance. Other mechanisms include BCR-ABLI amplification, overexpression of the SRC family of kinases, and pharmacokinetic and pharmacodynamic factors. CONCLUSIONS: Although not all resistance mechanisms have been identified and understood, several agents based on the known mechanisms have already been designed and developed and are beginning clinical trials.
Authors: Frank S Ong; Kingshuk Das; Jay Wang; Hana Vakil; Jane Z Kuo; Wendell-Lamar B Blackwell; Stephen W Lim; Mark O Goodarzi; Kenneth E Bernstein; Jerome I Rotter; Wayne W Grody Journal: Expert Rev Mol Diagn Date: 2012-07 Impact factor: 5.225
Authors: Luciene Terezina de Lima; Douglas Vivona; Carolina Tosin Bueno; Rosario D C Hirata; Mario H Hirata; André D Luchessi; Fabíola Attié de Castro; Maria de Lourdes F Chauffaille; Maria A Zanichelli; Carlos S Chiattone; Vania T M Hungria; Elvira M Guerra-Shinohara Journal: Med Oncol Date: 2014-01-29 Impact factor: 3.064
Authors: Sabine Cerny-Reiterer; Viviane Ghanim; Gregor Hoermann; Karl J Aichberger; Harald Herrmann; Leonhard Muellauer; Andreas Repa; Christian Sillaber; Andrew F Walls; Matthias Mayerhofer; Peter Valent Journal: Neoplasia Date: 2012-07 Impact factor: 5.715