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

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

Research output: Contribution to journalArticle

21 Citations (Scopus)

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 use a time-consuming sample exchange process with reference laboratories for IS calibration. A World Health Organization (WHO) BCR-ABL1 reference panel was developed (MR 1 -MR 4), but access to the material is limited. In this study, we describe the development of the first cell-based secondary reference panel that is traceable to and faithfully replicates the WHO panel, with an additional MR 4.5 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 MR 4.5 sensitivity, and 58% obtained IS conversion factors from the secondary reference concordant with their current values. 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.

Original languageEnglish (US)
Pages (from-to)1844-1852
Number of pages9
JournalLeukemia
Volume30
Issue number9
DOIs
StatePublished - Sep 1 2016

Fingerprint

Calibration
Polymerase Chain Reaction
Withholding Treatment
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Disease Management
Genes

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Cite this

Cross, N. C. P., White, H. E., Ernst, T., Welden, L., Dietz, C., Saglio, G., ... Branford, S. (2016). Development and evaluation of a secondary reference panel for BCR-ABL1 quantification on the International Scale. Leukemia, 30(9), 1844-1852. https://doi.org/10.1038/leu.2016.90

Development and evaluation of a secondary reference panel for BCR-ABL1 quantification on the International Scale. / Cross, N. C P; White, H. E.; Ernst, T.; Welden, L.; Dietz, C.; Saglio, G.; 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, Richard; Qin, Y. Z.; Radich, J.; Sacha, T.; Touloumenidou, T.; Waits, P.; Wilkinson, E.; Zadro, R.; Müller, M. C.; Hochhaus, A.; Branford, S.

In: Leukemia, Vol. 30, No. 9, 01.09.2016, p. 1844-1852.

Research output: Contribution to journalArticle

Cross, NCP, White, HE, Ernst, T, Welden, L, Dietz, C, Saglio, G, Mahon, FX, Wong, CC, Zheng, D, Wong, S, Wang, SS, Akiki, S, Albano, F, Andrikovics, H, Anwar, J, Balatzenko, G, Bendit, I, Beveridge, J, Boeckx, N, Cerveira, N, Cheng, SM, Colomer, D, Czurda, S, Daraio, F, Dulucq, S, Eggen, L, El Housni, H, Gerrard, G, Gniot, M, Izzo, B, Jacquin, D, Janssen, JJWM, Jeromin, S, Jurcek, T, Kim, DW, Machova-Polakova, K, Martinez-Lopez, J, McBean, M, Mesanovic, S, Mitterbauer-Hohendanner, G, Mobtaker, H, Mozziconacci, MJ, Pajič, T, Pallisgaard, N, Panagiotidis, P, Press, R, Qin, YZ, Radich, J, Sacha, T, Touloumenidou, T, Waits, P, Wilkinson, E, Zadro, R, Müller, MC, Hochhaus, A & Branford, S 2016, 'Development and evaluation of a secondary reference panel for BCR-ABL1 quantification on the International Scale', Leukemia, vol. 30, no. 9, pp. 1844-1852. https://doi.org/10.1038/leu.2016.90
Cross, N. C P ; White, H. E. ; Ernst, T. ; Welden, L. ; Dietz, C. ; Saglio, G. ; 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, Richard ; Qin, Y. Z. ; Radich, J. ; Sacha, T. ; Touloumenidou, T. ; Waits, P. ; Wilkinson, E. ; Zadro, R. ; Müller, M. C. ; Hochhaus, A. ; Branford, S. / Development and evaluation of a secondary reference panel for BCR-ABL1 quantification on the International Scale. In: Leukemia. 2016 ; Vol. 30, No. 9. pp. 1844-1852.
@article{8df3e14f3de446739c33832ec7cb0d24,
title = "Development and evaluation of a secondary reference panel for BCR-ABL1 quantification on the International Scale",
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 use a time-consuming sample exchange process with reference laboratories for IS calibration. A World Health Organization (WHO) BCR-ABL1 reference panel was developed (MR 1 -MR 4), but access to the material is limited. In this study, we describe the development of the first cell-based secondary reference panel that is traceable to and faithfully replicates the WHO panel, with an additional MR 4.5 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 MR 4.5 sensitivity, and 58{\%} obtained IS conversion factors from the secondary reference concordant with their current values. 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.",
author = "Cross, {N. C P} and White, {H. E.} and T. Ernst and L. Welden and C. Dietz and G. Saglio and Mahon, {F. X.} and Wong, {C. C.} and D. Zheng and S. Wong and Wang, {S. S.} and S. Akiki and F. Albano and H. Andrikovics and J. Anwar and G. Balatzenko and I. Bendit and J. Beveridge and N. Boeckx and N. Cerveira and Cheng, {S. M.} and D. Colomer and S. Czurda and F. Daraio and S. Dulucq and L. Eggen and {El Housni}, H. and G. Gerrard and M. Gniot and B. Izzo and D. Jacquin and Janssen, {J. J W M} and S. Jeromin and T. Jurcek and Kim, {D. W.} and K. Machova-Polakova and J. Martinez-Lopez and M. McBean and S. Mesanovic and G. Mitterbauer-Hohendanner and H. Mobtaker and Mozziconacci, {M. J.} and T. Pajič and N. Pallisgaard and P. Panagiotidis and Richard Press and Qin, {Y. Z.} and J. Radich and T. Sacha and T. Touloumenidou and P. Waits and E. Wilkinson and R. Zadro and M{\"u}ller, {M. C.} and A. Hochhaus and S. Branford",
year = "2016",
month = "9",
day = "1",
doi = "10.1038/leu.2016.90",
language = "English (US)",
volume = "30",
pages = "1844--1852",
journal = "Leukemia",
issn = "0887-6924",
publisher = "Nature Publishing Group",
number = "9",

}

TY - JOUR

T1 - Development and evaluation of a secondary reference panel for BCR-ABL1 quantification on the International Scale

AU - Cross, N. C P

AU - White, H. E.

AU - Ernst, T.

AU - Welden, L.

AU - Dietz, C.

AU - Saglio, G.

AU - Mahon, F. X.

AU - Wong, C. C.

AU - Zheng, D.

AU - Wong, S.

AU - Wang, S. S.

AU - Akiki, S.

AU - Albano, F.

AU - Andrikovics, H.

AU - Anwar, J.

AU - Balatzenko, G.

AU - Bendit, I.

AU - Beveridge, J.

AU - Boeckx, N.

AU - Cerveira, N.

AU - Cheng, S. M.

AU - Colomer, D.

AU - Czurda, S.

AU - Daraio, F.

AU - Dulucq, S.

AU - Eggen, L.

AU - El Housni, H.

AU - Gerrard, G.

AU - Gniot, M.

AU - Izzo, B.

AU - Jacquin, D.

AU - Janssen, J. J W M

AU - Jeromin, S.

AU - Jurcek, T.

AU - Kim, D. W.

AU - Machova-Polakova, K.

AU - Martinez-Lopez, J.

AU - McBean, M.

AU - Mesanovic, S.

AU - Mitterbauer-Hohendanner, G.

AU - Mobtaker, H.

AU - Mozziconacci, M. J.

AU - Pajič, T.

AU - Pallisgaard, N.

AU - Panagiotidis, P.

AU - Press, Richard

AU - Qin, Y. Z.

AU - Radich, J.

AU - Sacha, T.

AU - Touloumenidou, T.

AU - Waits, P.

AU - Wilkinson, E.

AU - Zadro, R.

AU - Müller, M. C.

AU - Hochhaus, A.

AU - Branford, S.

PY - 2016/9/1

Y1 - 2016/9/1

N2 - 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 use a time-consuming sample exchange process with reference laboratories for IS calibration. A World Health Organization (WHO) BCR-ABL1 reference panel was developed (MR 1 -MR 4), but access to the material is limited. In this study, we describe the development of the first cell-based secondary reference panel that is traceable to and faithfully replicates the WHO panel, with an additional MR 4.5 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 MR 4.5 sensitivity, and 58% obtained IS conversion factors from the secondary reference concordant with their current values. 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.

AB - 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 use a time-consuming sample exchange process with reference laboratories for IS calibration. A World Health Organization (WHO) BCR-ABL1 reference panel was developed (MR 1 -MR 4), but access to the material is limited. In this study, we describe the development of the first cell-based secondary reference panel that is traceable to and faithfully replicates the WHO panel, with an additional MR 4.5 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 MR 4.5 sensitivity, and 58% obtained IS conversion factors from the secondary reference concordant with their current values. 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.

UR - http://www.scopus.com/inward/record.url?scp=84973097794&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84973097794&partnerID=8YFLogxK

U2 - 10.1038/leu.2016.90

DO - 10.1038/leu.2016.90

M3 - Article

C2 - 27109508

AN - SCOPUS:84973097794

VL - 30

SP - 1844

EP - 1852

JO - Leukemia

JF - Leukemia

SN - 0887-6924

IS - 9

ER -