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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 van Dongen, Jacques J. M. Langerak, A W Brüggemann, M Evans, P A S Hummel, M Lavender, F L Delabesse, E Davi, F Schuuring, E García Sanz, Ramón van Krieken, J H J M Droese, J González, D Bastard, C White, H E Spaargaren, M González Díaz, Marcos Parreira, A Smith, J L Morgan, G J Kneba, M Macintyre, E A Lymphoma Rearrangement Immunoglobulin T-cell receptor Monoclonality Chromosome Aberrations Lymphoproliferative Disorders European Union Clone Cells DNA Primers Gene Rearrangement Humans Polymerase Chain Reaction Reference Standards Reproducibility of Results Immunoglobulins 3205.04 Hematología reacción en cadena de la polimerasa humanos trastornos linfoproliferativos reproducibilidad de resultados células clonales aberraciones cromosómicas inmunoglobulinas cebadores de ADN estándares de referencia reordenamiento génico Unión Europea Es el artículo principal en el desarrollo, estandarización y aplicación de la biología molecular para el diagnóstico de clonalidad en síndromes linfoproliferativos B y T. Hoy en día, práctica-mente todos los diagnósticos de linfomas y Síndromes relacionados que se diagnostican en Europa y en USA utilizan esta metodología como ayuda para en el diagnóstico definitivo. [EN]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 TCRgammadelta(+) 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. Hospital Universitario de Salamanca Universidad de Salamamnca Hospital Universitario de Salamanca 2024-02-05T10:21:49Z 2024-02-05T10:21:49Z 2003-12 2099-12-31 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion van Dongen, Langerak, Brüggemann, Evans, Hummel, Lavender, Delabesse, Davi, Schuuring, García-Sanz, van Krieken, Droese, González, Bastard, White, Spaargaren, González, Parreira, Smith, et al. (2003). [Rev. of 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, 17(12), 2257-2317. https://doi.org/10.1038/SJ.LEU.2403202 0887-6924 http://hdl.handle.net/10366/155309 10.1038/sj.leu.2403202 14671650 1476-5551 eng https://doi.org/10.1038/SJ.LEU.2403202 BIOMED-2 Concerted Action BMH4-CT98-3936 Attribution-NonCommercial-NoDerivatives 4.0 Internacional http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/embargoedAccess Springer Nature https://gredos.usal.es/bitstream/10366/155309/4/2003-14671650%20Van%20Dongen%2c%20Leukemia.pdf.jpg Hispana TEXT http://creativecommons.org/licenses/by/4.0/ Gredos. Repositorio Documental de la Universidad de Salamanca http://hdl.handle.net/10366/155309