title: BCR-ABL1 expression, RT-qPCR and treatment decisions in chronic myeloid leukaemia.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Haematology & Genetic Pathology, School of Medicine, Flinders University and Medical Centre, Bedford Park, South Australia, Australia.
authors.forename: Susan
authors.initials: S
authors.lastname: Latham
authors.affiliation: Department of Haematology & Genetic Pathology, School of Medicine, Flinders University and Medical Centre, Bedford Park, South Australia, Australia.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Bartley
authors.affiliation: Department of Haematology & Genetic Pathology, School of Medicine, Flinders University and Medical Centre, Bedford Park, South Australia, Australia.
authors.forename: Bradley
authors.initials: B
authors.lastname: Budgen
authors.affiliation: Department of Haematology & Genetic Pathology, School of Medicine, Flinders University and Medical Centre, Bedford Park, South Australia, Australia Haematology Division, SA Pathology, Adelaide, South Australia, Australia.
authors.forename: David M
authors.initials: DM
authors.lastname: Ross
authors.affiliation: Department of Haematology & Genetic Pathology, School of Medicine, Flinders University and Medical Centre, Bedford Park, South Australia, Australia.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hughes
authors.affiliation: Centre for Cancer Biology, SA Pathology, Adelaide, South Australia, Australia.
authors.forename: Susan
authors.initials: S
authors.lastname: Branford
authors.affiliation: South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
authors.forename: Deborah
authors.initials: D
authors.lastname: White
authors.affiliation: Haematology Division, SA Pathology, Adelaide, South Australia, Australia.
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Hughes
authors.affiliation: Department of Haematology & Genetic Pathology, School of Medicine, Flinders University and Medical Centre, Bedford Park, South Australia, Australia Monoquant Pty Ltd, Adelaide, South Australia, Australia.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Morley
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D000066491:Clinical Decision-Making; D016044:Fusion Proteins, bcr-abl / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D000068877:Imatinib Mesylate / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D018365:Neoplasm, Residual / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D011743:Pyrimidines / Q000627:therapeutic use; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000970:Antineoplastic Agents; C581634:BCR-ABL1 fusion protein, human; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; C498826:nilotinib
keywords: CANCER GENETICS; CML; PCR