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T-lymphocytes in bone marrow samples of children with acute lymphoblastic leukemia during and after chemotherapy might hamper PCR-based minimal residual disease studies

Leukemia volume 15, pages 1301–1302 (2001)Cite this article

Analysis of minimal residual disease (MRD) during the first phases of treatment can predict outcome in children with acute lymphoblastic leukemia (ALL).1 Sensitive MRD detection is possible in the majority of ALL patients by PCR analysis of clonal rearrangements of immunoglobulin (Ig) and T cell receptor (TCR) genes.2 The sensitivity of these PCR targets however is at least partly dependent on the frequency of comparable gene rearrangements in normal cells. This is particularly true for TCR gamma (TCRG) gene rearrangements, because they occur on both alleles in virtually all CD3+ T-lymphocytes and show limited combinatorial and junctional diversity. Since TCRG gene rearrangements occur in approximately 55% of precursor-B-ALL and in approximately 90% of T-ALL, they are however widely used as PCR targets in MRD studies of ALL patients.2,3

Recently, Delabesse et al4 reported their rapid and elegant multifluorescent TCRG Vγ and Jγ gene scanning for detection of moderate levels of MRD without the usage of junctional region specific oligonucleotides. For sensitivity testing, they evaluated six TCRG gene rearrangements from three T-ALLs by multiplex and Vγ-Jγ specific direct fluorescent PCR in dilution experiments using DNA from a mixture of 10% peripheral blood (PB) in the U937 myeloid cell line to simulate early remission bone marrow conditions. We wonder whether this is the correct test condition for sensitivity testing, because such an artificial mixture of 10% PB contains only 6–8% CD3+ T-lymphocytes. In normal bone marrow (BM) the mean frequency of CD7+ cells is indeed 7.9 ± 1.8% in children less than 14 years of age and ±86% of them are CD3+ T-lymphocytes.5 However, BM samples obtained during and after chemotherapy for ALL in children differ significantly from normal BM samples, particularly just after induction treatment.6

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References

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Authors and Affiliations

  1. Dutch Childhood Leukemia Study Group, The Hague, The Netherlands

    ER van Wering & BEM van der Linden-Schrever

  2. Department of Immunology, University Hospital, Rotterdam/Erasmus University, Rotterdam, The Netherlands

    VHJ van der Velden, T Szczepański & JJM van Dongen

  3. Department of Pediatric Hematology and Chemotherapy, Silesian Medical Academy, Zabrze, Poland

    T Szczepański

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van Wering, E., van der Linden-Schrever, B., van der Velden, V. et al. T-lymphocytes in bone marrow samples of children with acute lymphoblastic leukemia during and after chemotherapy might hamper PCR-based minimal residual disease studies. Leukemia 15, 1301–1302 (2001). https://doi.org/10.1038/sj.leu.2402184

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