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Minimal Residual Disease

Drug-induced immunophenotypic modulation in childhood ALL: implications for minimal residual disease detection

Leukemia volume 19, pages 49–56 (2005)Cite this article

Abstract

Assessment of minimal residual disease (MRD) by flow cytometry is considered to be based on the reproducibility of the leukemic immunophenotype detected at diagnosis. However, we previously noticed modulation of surface antigen expression in acute lymphoblastic leukemia (ALL) during the early treatment. Hence, we investigated this in 30 children with B-cell precursor ALL consecutively enrolled in the AIEOP-BFM ALL 2000 protocol. Quantitative expression of seven antigens useful in MRD monitoring was studied at diagnosis and compared to that measured at different time points of remission induction therapy. Downmodulation in the expression of CD10 and CD34 occurred at follow-up. By contrast, upmodulation of CD19, CD20, CD45RA, and CD11a was observed, while the expression of CD58 remained stable. Despite this, we could unambiguously discriminate leukemic cells from normal residual B cells. This holds true when bone marrow (BM) samples from similarly treated T-ALL patients, but not from healthy donors, were used as reference. Our results indicate that immunophenotypic modulation occurs in ALL during the early phases of BFM-type protocols. However, the accuracy of MRD detection by flow cytometry seems not negatively affected if adequate analysis protocols are employed. Investigators should take this phenomenon into account in order to avoid pitfalls in flow cytometric MRD studies.

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Acknowledgements

We thank Giovanni Giudici for his excellent technical assistance with cytogenetic studies, the MRD core-group for the PCR-based MRD data, and the physician and nurses of the Monza's Pediatric Department for their continued support. This work was supported by the Fondazione M Tettamanti and by the Associazione Italiana per la Ricerca sul Cancro (AIRC), Fondazione Città della Speranza, Fondazione Cariplo. The study was promoted by the International BFM-Study Group under the direction of G Masera, H Gadner, and M Schrappe.

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Authors and Affiliations

  1. Centro Ricerca M Tettamanti, Clinica Pediatrica Università Milano-Bicocca, Ospedale San Gerardo, Monza (MI), Italy

    G Gaipa, O Maglia, V Leoni, G Cazzaniga, C Bugarin, T Coliva & A Biondi

  2. Dipartimento di Pediatria, Università di Padova, Padova, Italy

    G Basso, M Veltroni & B Michelotto

  3. Dipartimento di Medicina Clinica, Prevenzione e Biotecnologie Sanitarie, Facolta’ di Medicina e Chirurgia, Università di Milano-Bicocca, Monza (MI), Italy

    A Faini, M G Valsecchi & A Biondi

  4. Charite University Medicine Berlin, Campus Buch, Robert-Rössle-Clinic, Helios Klinikum, Berlin, Germany

    R Ratei

  5. Children's Cancer Research Institute, St Anna Children's Hospital, Vienna, Austria

    M N Dworzak

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  1. G Gaipa
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  2. G Basso
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  3. O Maglia
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  6. G Cazzaniga
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on behalf of the I-BFM-ALL-FCM-MRD-Study Group

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Correspondence to A Biondi.

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Gaipa, G., Basso, G., Maglia, O. et al. Drug-induced immunophenotypic modulation in childhood ALL: implications for minimal residual disease detection. Leukemia 19, 49–56 (2005). https://doi.org/10.1038/sj.leu.2403559

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