Significantly improved PCR-based clonality testing in B-cell malignancies by use of multiple immunoglobulin gene targets

Report of the BIOMED-2 Concerted Action BHM4-CT98-3936

P. A. S. Evans, Ch Pott, P. J. T. A. Groenen, G. Salles, F. Davi, F. Berger, J. F. Garcia, J. H. J. M. van Krieken, S. Pals, Ph Kluin, E. Schuuring, M. Spaargaren, E. Boone, D. Gonzalez, B. Martinez, R. Villuendas, P. Gameiro, T. C. Diss, K. Mills, G. J. Morgan & 13 others G. I. Carter, Benedict J Milner, D. Pearson, M. Hummel, W. Jung, M. Ott, D. Canioni, K. Beldjord, C. Bastard, M. H. Delfau-Larue, J. J. M. van Dongen, T. J. Molina, J. Cabecadas

Research output: Contribution to journalArticle

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Abstract

Polymerase chain reaction (PCR) assessment of clonal immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements is an important diagnostic tool in mature B-cell neoplasms. However, lack of standardized PCR protocols resulting in a high level of false negativity has hampered comparability of data in previous clonality studies. In order to address these problems, 22 European laboratories investigated the Ig/TCR rearrangement patterns as well as t(14; 18) and t( 11; 14) translocations of 369 B-cell malignancies belonging to five WHO-defined entities using the standardized BIOMED-2 multiplex PCR tubes accompanied by international pathology panel review. B-cell clonality was detected by combined use of the IGH and IGK multiplex PCR assays in all 260 definitive cases of B-cell chronic lymphocytic leukemia (n = 56), mantle cell lymphoma ( n 54), marginal zone lymphoma ( n 41) and follicular lymphoma ( n 109). Two of 109 cases of diffuse large B-cell lymphoma showed no detectable clonal marker. The use of these techniques to assign cell lineage should be treated with caution as additional clonal TCR gene rearrangements were frequently detected in all disease categories. Our study indicates that the BIOMED-2 multiplex PCR assays provide a powerful strategy for clonality assessment in B-cell malignancies resulting in high Ig clonality detection rates particularly when IGH and IGK strategies are combined.

Original languageEnglish
Pages (from-to)207-214
Number of pages8
JournalLeukemia
Volume21
Issue number2
Early online date14 Dec 2006
DOIs
Publication statusPublished - Feb 2007

Keywords

  • clonality
  • PCR
  • B-cell malignancies
  • Ig rearrangements
  • TCR rearrangements
  • BIOMED-2
  • polymerase-chain-reaction
  • incomplete DJH rearrangements
  • minimal residual disease
  • chromosomal translocation
  • somatic hypermutation
  • lymphomas
  • myeloma
  • locus
  • frequency
  • T(14-18)

Cite this

Significantly improved PCR-based clonality testing in B-cell malignancies by use of multiple immunoglobulin gene targets : Report of the BIOMED-2 Concerted Action BHM4-CT98-3936. / Evans, P. A. S.; Pott, Ch; Groenen, P. J. T. A.; Salles, G.; Davi, F.; Berger, F.; Garcia, J. F.; van Krieken, J. H. J. M.; Pals, S.; Kluin, Ph; Schuuring, E.; Spaargaren, M.; Boone, E.; Gonzalez, D.; Martinez, B.; Villuendas, R.; Gameiro, P.; Diss, T. C.; Mills, K.; Morgan, G. J.; Carter, G. I.; Milner, Benedict J; Pearson, D.; Hummel, M.; Jung, W.; Ott, M.; Canioni, D.; Beldjord, K.; Bastard, C.; Delfau-Larue, M. H.; van Dongen, J. J. M.; Molina, T. J.; Cabecadas, J.

In: Leukemia, Vol. 21, No. 2, 02.2007, p. 207-214.

Research output: Contribution to journalArticle

Evans, PAS, Pott, C, Groenen, PJTA, Salles, G, Davi, F, Berger, F, Garcia, JF, van Krieken, JHJM, Pals, S, Kluin, P, Schuuring, E, Spaargaren, M, Boone, E, Gonzalez, D, Martinez, B, Villuendas, R, Gameiro, P, Diss, TC, Mills, K, Morgan, GJ, Carter, GI, Milner, BJ, Pearson, D, Hummel, M, Jung, W, Ott, M, Canioni, D, Beldjord, K, Bastard, C, Delfau-Larue, MH, van Dongen, JJM, Molina, TJ & Cabecadas, J 2007, 'Significantly improved PCR-based clonality testing in B-cell malignancies by use of multiple immunoglobulin gene targets: Report of the BIOMED-2 Concerted Action BHM4-CT98-3936', Leukemia, vol. 21, no. 2, pp. 207-214. https://doi.org/10.1038/sj.leu.2404479
Evans, P. A. S. ; Pott, Ch ; Groenen, P. J. T. A. ; Salles, G. ; Davi, F. ; Berger, F. ; Garcia, J. F. ; van Krieken, J. H. J. M. ; Pals, S. ; Kluin, Ph ; Schuuring, E. ; Spaargaren, M. ; Boone, E. ; Gonzalez, D. ; Martinez, B. ; Villuendas, R. ; Gameiro, P. ; Diss, T. C. ; Mills, K. ; Morgan, G. J. ; Carter, G. I. ; Milner, Benedict J ; Pearson, D. ; Hummel, M. ; Jung, W. ; Ott, M. ; Canioni, D. ; Beldjord, K. ; Bastard, C. ; Delfau-Larue, M. H. ; van Dongen, J. J. M. ; Molina, T. J. ; Cabecadas, J. / Significantly improved PCR-based clonality testing in B-cell malignancies by use of multiple immunoglobulin gene targets : Report of the BIOMED-2 Concerted Action BHM4-CT98-3936. In: Leukemia. 2007 ; Vol. 21, No. 2. pp. 207-214.
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abstract = "Polymerase chain reaction (PCR) assessment of clonal immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements is an important diagnostic tool in mature B-cell neoplasms. However, lack of standardized PCR protocols resulting in a high level of false negativity has hampered comparability of data in previous clonality studies. In order to address these problems, 22 European laboratories investigated the Ig/TCR rearrangement patterns as well as t(14; 18) and t( 11; 14) translocations of 369 B-cell malignancies belonging to five WHO-defined entities using the standardized BIOMED-2 multiplex PCR tubes accompanied by international pathology panel review. B-cell clonality was detected by combined use of the IGH and IGK multiplex PCR assays in all 260 definitive cases of B-cell chronic lymphocytic leukemia (n = 56), mantle cell lymphoma ( n 54), marginal zone lymphoma ( n 41) and follicular lymphoma ( n 109). Two of 109 cases of diffuse large B-cell lymphoma showed no detectable clonal marker. The use of these techniques to assign cell lineage should be treated with caution as additional clonal TCR gene rearrangements were frequently detected in all disease categories. Our study indicates that the BIOMED-2 multiplex PCR assays provide a powerful strategy for clonality assessment in B-cell malignancies resulting in high Ig clonality detection rates particularly when IGH and IGK strategies are combined.",
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AU - Groenen, P. J. T. A.

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AU - Davi, F.

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AU - Garcia, J. F.

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KW - TCR rearrangements

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KW - polymerase-chain-reaction

KW - incomplete DJH rearrangements

KW - minimal residual disease

KW - chromosomal translocation

KW - somatic hypermutation

KW - lymphomas

KW - myeloma

KW - locus

KW - frequency

KW - T(14-18)

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