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BCR-ABL1 expression, RT-qPCR and treatment decisions in chronic myeloid leukaemia
  1. Susan Latham1,
  2. Paul A Bartley1,
  3. Bradley Budgen1,
  4. David M Ross1,2,
  5. Elizabeth Hughes1,
  6. Susan Branford3,
  7. Deborah White4,
  8. Timothy P Hughes2,
  9. Alexander A Morley1,5
  1. 1Department of Haematology & Genetic Pathology, School of Medicine, Flinders University and Medical Centre, Bedford Park, South Australia, Australia
  2. 2Haematology Division, SA Pathology, Adelaide, South Australia, Australia
  3. 3Centre for Cancer Biology, SA Pathology, Adelaide, South Australia, Australia
  4. 4South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia
  5. 5Monoquant Pty Ltd, Adelaide, South Australia, Australia
  1. Correspondence to Professor Alexander Morley, Department of Haematology and Genetic Pathology, Flinders University, Bedford Park, SA 5042, Australia; alec.morley{at}flinders.edu.au

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.

  • CML
  • PCR
  • CANCER GENETICS

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