Implications of BCR-ABL1 kinase domain-mediated resistance in chronic myeloid leukemia

• Published in: Leukemia research Vol. 38; no. 1; pp. 10 - 20
• Main Authors: Soverini, Simona, Branford, Susan, Nicolini, Franck E., Talpaz, Moshe, Deininger, Michael W.N., Martinelli, Giovanni, Müller, Martin C., Radich, Jerald P., Shah, Neil P.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.01.2014
• Subjects: BCR-ABL1; Chronic myeloid leukemia; DNA Mutational Analysis - methods; DNA Mutational Analysis - trends; Drug Resistance, Neoplasm - genetics; Forecasting; Fusion Proteins, bcr-abl - genetics; Hematology, Oncology and Palliative Medicine; Humans; Kinase domain; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics; Mutation; Mutations; Philadelphia chromosome; Practice Guidelines as Topic; Prognosis; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Resistance; Tyrosine kinase inhibitors; Resistance; Mutations; BCR-ABL1; Kinase domain; Chronic myeloid leukemia; Tyrosine kinase inhibitors; Philadelphia chromosome
• ISSN: 0145-2126; 1873-5835; 1873-5835
• DOI: 10.1016/j.leukres.2013.09.011

Patients with chronic myeloid leukemia develop resistance to both first-generation and second-generation tyrosine kinase inhibitors (TKIs) as a result of mutations in the kinase domain (KD) of BCR-ABL1. A wide range of BCR-ABL1 KD mutations that confer resistance to TKIs have been identified, and the T315I mutant has proven particularly difficult to target. This review summarizes the prevalence, impact, and prognostic implications of BCR-ABL1 KD mutations in patients with chronic myeloid leukemia who are treated with current TKIs and provides an overview of recent treatment guidelines and future trends for the detection of mutations.