Many BCR-ABL1 compound mutations reported in chronic myeloid leukemia patients may actually be artifacts due to PCR-mediated recombination
Date
2014
Authors
Parker, W.
Phillis, S.
Yeung, D.
Hughes, T.
Scott, H.
Branford, S.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Blood, 2014; 124(1):153-155
Statement of Responsibility
Wendy T. Parker, Stuart R. Phillis, David T. O. Yeung, Timothy P. Hughes, Hamish S. Scott, and Susan Branford
Conference Name
Abstract
BCR-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.
School/Discipline
Dissertation Note
Provenance
Description
Letter to the editor
Access Status
Rights
© 2014 by The American Society of Hematology