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Development and evaluation of a secondary reference panel for BCR-ABL1 quantitation on the International Scale

Development and evaluation of a secondary reference panel for BCR-ABL1 quantitation on the International Scale
Development and evaluation of a secondary reference panel for BCR-ABL1 quantitation on the International Scale
Molecular monitoring of chronic myeloid leukemia patients using robust BCR-ABL1 tests standardized to the International Scale (IS) is key to proper disease management, especially when treatment cessation is considered. Most laboratories currently utilize a time-consuming sample exchange process with reference laboratories for IS calibration. A World Health Organization (WHO) BCR-ABL1 reference panel was developed (MR1-MR4), but access to the material is limited. In this study, we describe the development of the first cell-based secondary reference panel that’s traceable to and faithfully replicates the WHO panel, with an additional MR4.5 level. The secondary panel was calibrated to IS using digital PCR with ABL1, BCR, and GUSB as reference genes and evaluated by 44 laboratories worldwide. Interestingly, we found that >40% of BCR-ABL1 assays showed signs of inadequate optimization such as poor linearity and suboptimal PCR efficiency. Nonetheless, when optimized sample inputs were used, >60% demonstrated satisfactory IS accuracy, precision and/or MR4.5 sensitivity, and 58% obtained IS conversion factors from the secondary reference concordant with their current ones. Correlation analysis indicated no significant alterations in %BCR-ABL1 results caused by different assay configurations. More assays achieved good precision and/or sensitivity than IS accuracy, indicating the need for better IS calibration mechanisms.
0887-6924
1844-1852
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Cross, N.C.P.
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Hochhaus, A.
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Branford, S.
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Cross, N.C.P., White, H.E., Ernst, T., Welden, L., Dietz, C., Saglio, Guseppe, Mahon, F-X., Wong, C.C., Zheng, D., Wong, S., Wang, S-S., Akiki, S., Albano, F., Andrikovics, H., Anwar, J., Balatzenko, G., Bendit, I., Beveridge, J., Boeckx, N., Cerveira, N., Cheng, S-M., Colomer, D., Czurda, S., Daraio, F., Dulucq, S., Eggen, L., El Housni, H., Gerrard, G., Gniot, M., Izzo, B., Jacquin, D., Janssen, J.J.W.M., Jeromin, S., Jurcek, T., Kim, D-W., Machova-Polakova, K., Martinez-Lopez, J., McBean, M., Mesanovic, S., Mitterbauer-Hohendanner, G., Mobtaker, H., Mozziconacci, M-J., Pajič, T., Pallisgaard, N., Panagiotidis, P., Press, R.D., Qin, Y-Z., Radich, J., Sacha, T., Touloumenidou, T., Waits, P., Wilkinson, E., Zadro, R., Müller, M.C., Hochhaus, A. and Branford, S. (2016) Development and evaluation of a secondary reference panel for BCR-ABL1 quantitation on the International Scale. Leukemia, 30 (9), 1844-1852. (doi:10.1038/leu.2016.90).

Record type: Article

Abstract

Molecular monitoring of chronic myeloid leukemia patients using robust BCR-ABL1 tests standardized to the International Scale (IS) is key to proper disease management, especially when treatment cessation is considered. Most laboratories currently utilize a time-consuming sample exchange process with reference laboratories for IS calibration. A World Health Organization (WHO) BCR-ABL1 reference panel was developed (MR1-MR4), but access to the material is limited. In this study, we describe the development of the first cell-based secondary reference panel that’s traceable to and faithfully replicates the WHO panel, with an additional MR4.5 level. The secondary panel was calibrated to IS using digital PCR with ABL1, BCR, and GUSB as reference genes and evaluated by 44 laboratories worldwide. Interestingly, we found that >40% of BCR-ABL1 assays showed signs of inadequate optimization such as poor linearity and suboptimal PCR efficiency. Nonetheless, when optimized sample inputs were used, >60% demonstrated satisfactory IS accuracy, precision and/or MR4.5 sensitivity, and 58% obtained IS conversion factors from the secondary reference concordant with their current ones. Correlation analysis indicated no significant alterations in %BCR-ABL1 results caused by different assay configurations. More assays achieved good precision and/or sensitivity than IS accuracy, indicating the need for better IS calibration mechanisms.

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Accepted/In Press date: 25 April 2016
e-pub ahead of print date: 3 June 2016
Published date: September 2016
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 393370
URI: http://eprints.soton.ac.uk/id/eprint/393370
ISSN: 0887-6924
PURE UUID: 46c1278d-4e43-4763-98c7-1e9d84458b28
ORCID for N.C.P. Cross: ORCID iD orcid.org/0000-0001-5481-2555

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Date deposited: 25 Apr 2016 14:32
Last modified: 07 Oct 2020 04:22

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Contributors

Author: N.C.P. Cross ORCID iD
Author: H.E. White
Author: T. Ernst
Author: L. Welden
Author: C. Dietz
Author: Guseppe Saglio
Author: F-X. Mahon
Author: C.C. Wong
Author: D. Zheng
Author: S. Wong
Author: S-S. Wang
Author: S. Akiki
Author: F. Albano
Author: H. Andrikovics
Author: J. Anwar
Author: G. Balatzenko
Author: I. Bendit
Author: J. Beveridge
Author: N. Boeckx
Author: N. Cerveira
Author: S-M. Cheng
Author: D. Colomer
Author: S. Czurda
Author: F. Daraio
Author: S. Dulucq
Author: L. Eggen
Author: H. El Housni
Author: G. Gerrard
Author: M. Gniot
Author: B. Izzo
Author: D. Jacquin
Author: J.J.W.M. Janssen
Author: S. Jeromin
Author: T. Jurcek
Author: D-W. Kim
Author: K. Machova-Polakova
Author: J. Martinez-Lopez
Author: M. McBean
Author: S. Mesanovic
Author: G. Mitterbauer-Hohendanner
Author: H. Mobtaker
Author: M-J. Mozziconacci
Author: T. Pajič
Author: N. Pallisgaard
Author: P. Panagiotidis
Author: R.D. Press
Author: Y-Z. Qin
Author: J. Radich
Author: T. Sacha
Author: T. Touloumenidou
Author: P. Waits
Author: E. Wilkinson
Author: R. Zadro
Author: M.C. Müller
Author: A. Hochhaus
Author: S. Branford

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