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Reply to Gaipa et al

Leukemia volume 19, page 1858 (2005)Cite this article

Gaipa et al1 reported immunophenotypic modulation in a series of children with precursor-B-ALL, treated according to the AIEOP-BFM ALL 2000 protocol. In a comment on this paper we reported the same observation in children treated according to the DCOG ALL-9 protocol.2 In addition, we exposed blast cells of five different patients, obtained at diagnosis, during 96?h to four different cytotoxic drugs (MTT test) and observed a comparable immunophenotypic modulation as observed ex vivo in patients undergoing treatment. Furthermore, we observed a clear relation between cell death and modulation and therefore concluded that antigen modulation can be mimicked in vitro and might, at least in part, be caused by drug-induced cell death. In a reply to our paper, Gaipa et al2 do not fully agree with our conclusions.

Firstly, they mention that in the MTT culture system blast cells might not survive for 96?h without the support of a bone marrow-derived stroma layer and that spontaneous apoptosis may occur. We agree with Gaipa et al that the MTT test is not optimal for culturing ALL cells and that spontaneous apoptosis may occur. In fact, the mean viability of control cells (not exposed to drugs) after 96?h culture in the reported experiments was 69% (range 40–95%). These control cells also showed the characteristic immunophenotypic modulation, suggesting that the modulation process is related to general cell death, independent of the type of apoptotic signal.

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References

  1. Gaipa G, Basso G, Maglia O, Leoni V, Cazzaniga G, Bugarin C et al. Drug-induced immunophenotypic modulation in childhood ALL: implications for minimal residual disease detection. Leukemia 2005; 19: 49–56.

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  2. Van der Sluijs-Gelling AJ, van der Velden VHJ, Roeffen ETJM, Veerman AJP, van Wering ER . Immunophenotypic modulation in childhood precursor B-ALL can be mimicked in vitro and is related to the induction of cell death. Leukemia 2005, 19:1845–1847.

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  4. Diaz D, Prieto A, Barcenilla H, Monserrat J, Prieto P, Sánchez MA et al. Loss of lineage antigens is a common feature of apoptotic lymphocytes. J Leukoc Biol 2004; 76: 609–615.

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Authors and Affiliations

  1. Dutch Childhood Oncology Group, The Hague, The Netherlands

    A J van der Sluijs-Gelling, E T J M Roeffen, A J P Veerman & E R van Wering

  2. Department of Immunology, Erasmus MC, Rotterdam, The Netherlands

    V H J van der Velden

  3. Department Paediatric Hemato-Oncology, Vrije Universiteit, University Medical Centre, Amsterdam, The Netherlands

    A J P Veerman

Authors
  1. A J van der Sluijs-Gelling
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  2. V H J van der Velden
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  3. E T J M Roeffen
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  4. A J P Veerman
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  5. E R van Wering
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Corresponding author

Correspondence to E R van Wering.

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van der Sluijs-Gelling, A., van der Velden, V., Roeffen, E. et al. Reply to Gaipa et al. Leukemia 19, 1858 (2005). https://doi.org/10.1038/sj.leu.2403913

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