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Non-specific amplification of patient-specific Ig/TCR gene rearrangements depends on the time point during therapy: implications for minimal residual disease monitoring

Leukemia volume 22, pages 641–644 (2008)Cite this article

Several studies have shown that detection of minimal residual disease (MRD) has prognostic relevance in childhood and adult acute lymphoblastic leukemia (ALL), both at initial diagnosis, at relapse, and before stem cell transplantation. Consequently, MRD-based therapy stratification nowadays is being included in many ALL treatment protocols. In most clinical ALL studies, MRD is being evaluated by real-time quantitative PCR (RQ-PCR) analysis of immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements, which serve as patient-specific markers for the leukemic cells.

Recently, the European Study Group on MRD detection in ALL developed guidelines for the interpretation of RQ-PCR data,1 which are crucial for multi-center MRD studies.2 These guidelines include a definition of the ‘Quantitative Range’ (the reproducible part of the assay in which data can accurately and reliably be quantified) and definitions of MRD positivity. In these definitions, the presence and level of non-specific amplification (NSA) plays an important role. NSA is dependent on the Ig/TCR locus involved, the gene segments used and the number and type of deleted and inserted nucleotides in the junctional region. For example, NSA occurs in about 35% of IGH targets (particularly those using the JH4, JH5 or JH6 gene segment) and in over 90% of TCRG targets.3

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References

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  1. Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

    V H J van der Velden, J M Wijkhuijs & J J M van Dongen

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  1. V H J van der Velden
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  2. J M Wijkhuijs
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  3. J J M van Dongen
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Correspondence to V H J van der Velden.

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van der Velden, V., Wijkhuijs, J. & van Dongen, J. Non-specific amplification of patient-specific Ig/TCR gene rearrangements depends on the time point during therapy: implications for minimal residual disease monitoring. Leukemia 22, 641–644 (2008). https://doi.org/10.1038/sj.leu.2404925

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