title: A novel approach for BCR-ABL1 standardization to improve International Scale estimation.
abstract: BACKGROUND
  Standardization of BCR-ABL1 messenger RNA quantification by real-time PCR on the International Scale (IS) is critical for monitoring therapy response in chronic myelogenous leukaemia. Since 2006, BCR-ABL1 IS standardization is propagated along reference laboratories by calculating a laboratory-specific conversion factor (CF), co-ordinated in Europe through the European Treatment and Outcome Study project. Although this process has proven successful to some extent, it has not been achievable for all laboratories due to the complexity of the process and the stringent requirements in terms of numbers of samples to be exchanged. In addition, several BCR-ABL1 IS quantification methods and secondary reference materials became commercially available. However, it was observed that different IS methods generate consistently different results.
  
  
  METHODS
  To overcome these difficulties, we have developed an alternative and simple approach of CF calculation, based on the retrospective analysis of existing external quality assessment (EQA) data. Our approach does not depend on the exchange of samples and is solely based on the mathematical CF calculation using EQA results.
  
  
  CONCLUSIONS
  We have demonstrated by thorough statistical validation that this approach performs well in converting BCR-ABL1 measurements to improve IS estimation. In expectation of a true golden standard method for BCR-ABL1 IS quantification, the proposed method is a valuable alternative.
authors.affiliation: Laboratory for Molecular Diagnostics, Jessa Hospital, Hasselt, Belgium.
authors.forename: B
authors.initials: B
authors.lastname: Maes
authors.affiliation: Laboratory of Haematology, University Hospital Brussels, Brussels, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Bakkus
authors.affiliation: Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium.
authors.forename: N
authors.initials: N
authors.lastname: Boeckx
authors.affiliation: Laboratory for Molecular Diagnostics, AZ Delta, Roeselare, Belgium.
authors.forename: E
authors.initials: E
authors.lastname: Boone
authors.affiliation: Department of Laboratory Medicine, AZ Sint-Jan Brugge-Oostende AV, Brugge, Belgium.
authors.forename: B
authors.initials: B
authors.lastname: Cauwelier
authors.affiliation: Laboratory for Molecular Diagnostics - Haematology, University Hospital Gent, Gent, Belgium.
authors.forename: B
authors.initials: B
authors.lastname: Denys
authors.affiliation: Laboratory of Haematology, ZNA Antwerp, Antwerp, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: De Schouwer
authors.affiliation: Department of Haematology, University Hospitals, Leuven, Belgium.
authors.forename: T
authors.initials: T
authors.lastname: Devos
authors.affiliation: CUB Erasme, Brussels, Belgium.
authors.forename: H
authors.initials: H
authors.lastname: El Housni
authors.affiliation: Laboratory for Molecular Diagnostics, Jessa Hospital, Hasselt, Belgium.
authors.forename: F
authors.initials: F
authors.lastname: Hillen
authors.affiliation: Clinical Laboratory, AZ Sint-Lucas, Gent, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Jacobs
authors.affiliation: Laboratory for Molecular Diagnostics, Haemato-Oncology Unit, University Hospital Liege, Liege, Belgium.
authors.forename: F
authors.initials: F
authors.lastname: Lambert
authors.affiliation: Clinical Laboratory, AZ Sint-Lucas, Gent, Belgium.
authors.forename: H
authors.initials: H
authors.lastname: Louagie
authors.affiliation: Laboratory of Haematology, University Hospital of Antwerp, Antwerp, Belgium.
authors.forename: M-B
authors.initials: MB
authors.lastname: Maes
authors.affiliation: Laboratory for Molecular Diagnostics, OLV Ziekenhuis Aalst, Aalst, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Meeus
authors.affiliation: Laboratory for Molecular Diagnostics, AZ Delta, Roeselare, Belgium.
authors.forename: E
authors.initials: E
authors.lastname: Moreau
authors.affiliation: Department of Laboratory Medicine, AZ Sint-Jan Brugge-Oostende AV, Brugge, Belgium.
authors.forename: F
authors.initials: F
authors.lastname: Nollet
authors.affiliation: Novartis Pharma, Vilvoorde, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Peeters
authors.affiliation: Laboratoire de biologie moléculaire, Cliniques Universitaires Saint-Luc, Bruxelles, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Saussoy
authors.affiliation: Department of Molecular Diagnostics, GZA St-Augustinus, Wilrijk, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Van Lint
authors.affiliation: Laboratoire de biologie moléculaire, Cliniques Universitaires Saint-Luc, Bruxelles, Belgium.
authors.forename: J-L
authors.initials: JL
authors.lastname: Vaerman
authors.affiliation: Laboratory for Molecular Diagnostics, OLV Ziekenhuis Aalst, Aalst, Belgium.
authors.forename: F
authors.initials: F
authors.lastname: Vaeyens
authors.affiliation: Laboratory for Molecular Diagnostics - Haematology, University Hospital Gent, Gent, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Vandepoele
authors.affiliation: Institut de Pathologie et de Génétique, Gosselies, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Vannuffel
authors.affiliation: Department of Molecular Diagnostics, GZA St-Augustinus, Wilrijk, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Ver Elst
authors.affiliation: Laboratory of Haematology, University Hospital of Antwerp, Antwerp, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Vermeulen
authors.affiliation: Interuniversity Institute for Biostatistics and statistical Bioinformatics (I-BIOSTAT), University of Hasselt, Diepenbeek, Belgium.
authors.forename: R
authors.initials: R
authors.lastname: Bruyndonckx
mesh_terms: D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D005820:Genetic Testing; D007391:International Cooperation; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis* / Q000235:genetics; D008722:Methods; D015588:Observer Variation; D012333:RNA, Messenger / Q000032:analysis*; D012015:Reference Standards; D012189:Retrospective Studies
chemical_list: D012333:RNA, Messenger; D016044:Fusion Proteins, bcr-abl
keywords: 
  BCR-ABL1
  ; Chronic myelogenous leukaemia; International Scale; standardization; therapy monitoring