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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 accessAbstract
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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Cites
Somatic generation of antibody diversity
Tonegawa, S. (1983) · Nature · doi:10.1038/302575a0 · Cited by 4,005
False leukemia–lymphoma cell lines: an update on over 500 cell lines
Drexler, H. G., Dirks, W. G., Matsuo, Y., & MacLeod, R. A. F. (2003) · Leukemia · doi:10.1038/sj.leu.2402799 · Cited by 202
Cited by
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Kimura, H., Ito, Y., Kawabe, S., Gotoh, K., Takahashi, Y., Kojima, S., Naoe, T., Esaki, S., Kikuta, A., Sawada, A., et al. (2012) · Blood · doi:10.1182/blood-2011-10-381921 · Cited by 448
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Campbell, P. J., Pleasance, E. D., Stephens, P. J., Dicks, E., Rance, R., Goodhead, I., Follows, G. A., Green, A. R., Futreal, P. A., & Stratton, M. R. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0801523105 · Cited by 365
Murray, F., Darzentas, N., Hadzidimitriou, A., Tobin, G., Boudjogra, M., Scielzo, C., Laoutaris, N., Karlsson, K., Baran-Marzsak, F., Tsaftaris, A., et al. (2008) · Blood · doi:10.1182/blood-2007-07-099564 · Cited by 334
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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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