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T-Cell ALL: A Biomed 1 Cooperative Study

BIOMED-1 Concerted Action report: Flow cytometric characterization of CD7+ cell subsets in normal bone marrow as a basis for the diagnosis and follow-up of T cell acute lymphoblastic leukemia (T-ALL)

Leukemia volume 14, pages 816–825 (2000)Cite this article

Abstract

The European BIOMED-1 Concerted Action was initiated in 1994 to improve and standardize the flow cytometric detection of minimal residual disease (MRD) in acute leukemia (AL). Three different protocols were defined to identify the normal subsets of B, T and myeloid cells in bone marrow (BM), and were applied to the different types of AL in order to study aberrant immunophenotypes. Using sensitive acquisition methods (‘live gate’) T cell subsets in normal BM could be identified with five triple-stains: CD7/CD5/CD3, CD7/CD4/CD8, CD7/CD2/CD3, CD7/CD38/CD34 and TdT/CD7/surface or cytoplasmic (cy)CD3 (antibodies conjugated with FITC/PE/PECy5 or PerCP, respectively). The identification of T cell subsets in BM allowed definition of ‘empty spaces’ (ie areas of flow cytometric plots where normally no cells are found). All studied T-ALL cases (n = 65) were located in ‘empty spaces’ and could be discriminated from normal T cells. The most informative triple staining was TdT/CD7/cyCD3, which was aberrant in 91% of T-ALL cases. In most cases, two or more aberrant patterns were found. Apparently the immunophenotypes of T-ALL differ significantly from normal BM T cells. This is mostly caused by their thymocytic origin, but also the neoplastic transformation might have affected antigen expression patterns. Application of the five proposed marker combinations in T-ALL contributes to standardized detection of MRD, since cells persistent or reappearing in the ‘empty spaces’ can be easily identified in follow-up BM samples during and after treatment.

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Acknowledgements

This study was supported by European BIOMED-1 grant BMH1-CT94-1675, Swedish Cancer Society, Dutch Cancer Society/Koningin Wilhelimina Fonds (grant EUR 94-852), grant of the Associazione Italiana per la Ricerca sul Cancro, by Fondazione M Tettamanti, and a grant from ‘Liga Portuguesa contra o Cancro’. We thank Dakopatts (Glostrup, Denmark) and Caltag Lab (San Francisco, CA, USA) for providing charge-free reagents for the study and Mr Lewis G Edgel for editorial assistance.

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Author notes

  1. J Mazur: J Mazur was on leave from Department of Epidemiology and Health Care Planning, Institute Mother and Child, Warsaw, Poland.

Authors and Affiliations

  1. Department of Pathology, Karolinska Hospital, Stockholm, Sweden

    A Porwit-MacDonald, E Björklund & J Mazur

  2. Instituto Portugues de Oncologia, Lisboa, Portugal

    P Lucio & A Parreira

  3. Department of Immunology, Erasmus University, Rotterdam

    EG van Lochem, MWM van den Beemd & JJM van Dongen

  4. University Hospital, Rotterdam, The Netherlands

    EG van Lochem & MWM van den Beemd

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

    ER van Wering & E Baars

  6. Centro di Ricerca M Tettamanti, Monza, Italy

    G Gaipa & A Biondi

  7. Department of Hematology, University Hospital, Salamanca, Spain

    J Ciudad, JF San Miguel & A Orfao

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Porwit-MacDonald, A., Björklund, E., Lucio, P. et al. BIOMED-1 Concerted Action report: Flow cytometric characterization of CD7+ cell subsets in normal bone marrow as a basis for the diagnosis and follow-up of T cell acute lymphoblastic leukemia (T-ALL). Leukemia 14, 816–825 (2000). https://doi.org/10.1038/sj.leu.2401741

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