Compound Bcr-Abl1 Kinase Domain Mutants: Prevalence, Spectrum And Correlation With Tyrosine Kinase Inhibitor Resistance In A Prospective Series Of Philadelphia Chromosome-Positive Leukemia Patients Analyzed By Next Generation Sequencing

Next-Generation Sequencing (NGS)-based BCR-ABL1 kinase domain (KD) mutation screening has been shown to enable greater accuracy and sensitivity and straightforward identification of compound mutants (CM) as compared to Sanger sequencing (seq). However, the prevalence of CMs has never been assessed in prospective studies, and although in vitro data suggest that many of them may be challenging for all tyrosine kinase inhibitors (TKIs) including ponatinib, attempts to correlate such data with in vivo responses have never been made. To address these issues, we have reviewed the results of routine NGS-based BCR-ABL1 KD mutation screening performed over the past 3 years.