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Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: Report of the BIOMED-2 Concerted Action BMH4-CT98-3936

Open access
van Dongen, J J M, Langerak, A W, Brüggemann, M, Evans, P A S, Hummel, M, Lavender, F L, Delabesse, E, Davi, F, Schuuring, E, García-Sanz, R, van Krieken, J H J M, Droese, J, González, D, Bastard, C, White, H E, Spaargaren, M, González, M, Parreira, A, Smith, J L, Morgan, G J, Kneba, M, Macintyre, E A·2003·Leukemia

Abstract

In a European BIOMED-2 collaborative study, multiplex PCR assays have successfully been developed and standardized for the detection of clonally rearranged immunoglobulin (Ig) and T-cell receptor (TCR) genes and the chromosome aberrations t(11;14) and t(14;18). This has resulted in 107 different primers in only 18 multiplex PCR tubes: three VH–JH, two DH–JH, two Ig kappa (IGK), one Ig lambda (IGL), three TCR beta (TCRB), two TCR gamma (TCRG), one TCR delta (TCRD), three BCL1-Ig heavy chain (IGH), and one BCL2-IGH. The PCR products of Ig/TCR genes can be analyzed for clonality assessment by heteroduplex analysis or GeneScanning. The detection rate of clonal rearrangements using the BIOMED-2 primer sets is unprecedentedly high. This is mainly based on the complementarity of the various BIOMED-2 tubes. In particular, combined application of IGH (VH–JH and DH–JH) and IGK tubes can detect virtually all clonal B-cell proliferations, even in B-cell malignancies with high levels of somatic mutations. The contribution of IGL gene rearrangements seems limited. Combined usage of the TCRB and TCRG tubes detects virtually all clonal T-cell populations, whereas the TCRD tube has added value in case of TCRγδ+ T-cell proliferations. The BIOMED-2 multiplex tubes can now be used for diagnostic clonality studies as well as for the identification of PCR targets suitable for the detection of minimal residual disease.

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Metadata

Authors
van Dongen, J. J. M., Langerak, A. W., Brüggemann, M., Evans, P. A. S., Hummel, M., Lavender, F. L., Delabesse, E., Davi, F., Schuuring, E., García-Sanz, R., van Krieken, J. H. J. M., Droese, J., González, D., Bastard, C., White, H. E., Spaargaren, M., González, M., Parreira, A., Smith, J. L., Morgan, G. J., Kneba, M., & Macintyre, E. A.
Venue
Leukemia
Published
2003-12-01
Volume
17
Issue
12
Pages
2257-2317
ISSN
  • 0887-6924 (ISSN-L)
  • 1476-5551
OpenAlex
W2020094108
Cited by
3,043
References
2
FWCI
55.49
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: Report of the BIOMED-2 Concerted Action BMH4-CT98-3936. https://app.cochat.ai/papers/10.1038/sj.leu.2403202
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van Dongen, J. J. M., Langerak, A. W., Brüggemann, M., Evans, P. A. S., Hummel, M., Lavender, F. L., Delabesse, E., Davi, F., Schuuring, E., García-Sanz, R., van Krieken, J. H. J. M., Droese, J., González, D., Bastard, C., White, H. E., Spaargaren, M., González, M., Parreira, A., Smith, J. L., . . . Macintyre, E. A. (2003). Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: Report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia. https://doi.org/10.1038/sj.leu.2403202

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