Parker, W.Phillis, S.Yeung, D.Hughes, T.Scott, H.Branford, S.2015-03-182015-03-182014Blood, 2014; 124(1):153-1550006-49711528-0020http://hdl.handle.net/2440/90033Letter to the editorBCR-ABL1 kinase domain (KD) mutations are the most common known cause of treatment failure in chronic myeloid leukemia (CML). Emerging evidence suggests that compound mutations (>1 KD mutation in the same molecule) confer resistance to ponatinib and combination therapy (GNF-5/nilotinib). Surprisingly, however, in most cases reported, the same mutations were found both as compound mutations and as individual mutations in the same patient, suggesting that the same nucleotide substitution occurred independently multiple times within an individual patient. Based on extensive evidence that PCR frequently mediates recombination between highly similar templates and generates chimeric amplicons containing sequence from >1 different alleles, we argue that the mutant complexity reported maybe inflated due to PCR artifacts.en© 2014 by The American Society of HematologyFusion Proteins, bcr-ablPolymerase Chain ReactionMutationLeukemia, Myelogenous, Chronic, BCR-ABL PositiveArtifactsJournal article003001715510.1182/blood-2014-05-5734850003426183000232-s2.0-84903937403113988Yeung, D. [0000-0002-7558-9927]Hughes, T. [0000-0002-0910-3730] [0000-0002-7990-4509]Scott, H. [0000-0002-5813-631X]Branford, S. [0000-0002-1964-3626] [0000-0002-5095-7981]