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

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dc.contributor.authorLatham, S.
dc.contributor.authorBartley, P.
dc.contributor.authorBudgen, B.
dc.contributor.authorRoss, D.
dc.contributor.authorHughes, E.
dc.contributor.authorBranford, S.
dc.contributor.authorWhite, D.
dc.contributor.authorHughes, T.
dc.contributor.authorMorley, A.
dc.date.issued2016
dc.description.abstractRT-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.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.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.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.
dc.description.statementofresponsibilitySusan Latham, Paul A Bartley, Bradley Budgen, David M Ross, Elizabeth Hughes, Susan Branford, Deborah White, Timothy P Hughes, Alexander A Morley
dc.identifier.citationJournal of Clinical Pathology, 2016; 69(9):817-821
dc.identifier.doi10.1136/jclinpath-2015-203538
dc.identifier.issn0021-9746
dc.identifier.issn1472-4146
dc.identifier.orcidRoss, D. [0000-0001-7171-2935]
dc.identifier.orcidBranford, S. [0000-0002-1964-3626] [0000-0002-5095-7981]
dc.identifier.orcidWhite, D. [0000-0003-4844-333X]
dc.identifier.orcidHughes, T. [0000-0002-0910-3730] [0000-0002-7990-4509]
dc.identifier.urihttp://hdl.handle.net/2440/106037
dc.language.isoen
dc.publisherBMJ Publishing Group
dc.rights© 2016, BMJ Publishing Group Ltd and the Association of Clinical Pathologists
dc.source.urihttps://doi.org/10.1136/jclinpath-2015-203538
dc.subjectNeoplasm, Residual
dc.titleBCR-ABL1 expression, RT-qPCR and treatment decisions in chronic myeloid leukaemia
dc.typeJournal article
pubs.publication-statusPublished

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