BCR-ABL1 expression, RT-qPCR and treatment decisions in chronic myeloid leukaemia

Susan Latham, Paul Bartley, Brad Budgen, David Ross, Elizabeth Hughes, Susan Branford, Deborah White, Timothy Hughes, Alexander Morley

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    4 Citations (Scopus)

    Abstract

    Aims RT-qPCR is used to quantify minimal residual disease (MRD) in chronic myeloid leukaemia (CML) in order to make decisions on treatment, but its results depend on the level of BCR-ABL1 expression as well as leukaemic cell number. The aims of the study were to quantify inter-individual differences in expression level, to determine the relationship between expression level and response to treatment, and to investigate the effect of expression level on interpretation of the RT-qPCR result. Methods BCR-ABL1 expression was studied in 248 samples from 65 patients with CML by determining the difference between MRD quantified by RT-qPCR and DNA-qPCR. The results were analysed statistically and by simple indicative modelling. Results Inter-individual levels of expression approximated a normal distribution with an SD of 0.36 log. Expression at diagnosis correlated with expression during treatment. Response to treatment, as measured by the number of leukaemic cells after 3, 6 or 12 months of treatment, was not related to the level of expression. Indicative modelling suggested that interpretation of RT-qPCR results in relation to treatment guidelines could be affected by variation in expression when MRD was around 10% at 3 months and by both expression variation and Poisson variation when MRD was around or below the limit of detection of RT-qPCR. Conclusions Variation between individuals in expression of BCR-ABL1 can materially affect interpretation of the RT-qPCR when this test is used to make decisions on treatment.

    Original languageEnglish
    Pages (from-to)817-821
    Number of pages5
    JournalJournal of Molecular Diagnostics
    Volume69
    Issue number9
    DOIs
    Publication statusPublished - Sep 2016

    Keywords

    • cancer genetics
    • CML
    • PCR

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