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Enzyme and membrane markers in leukaemia: recent developments.

A V Hoffbrand, G Janossy

    Journal of Clinical Pathology
    |March 1, 1981
    PubMed
    Summary

    Terminal deoxynucleotidyl transferase (TdT) assays and immunofluorescence aid in distinguishing acute leukaemias. Adenosine deaminase (ADA) inhibition shows promise for treating T-cell acute lymphoblastic leukaemia (Thy-ALL).

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    Area of Science:

    • Hematology
    • Immunology
    • Oncology

    Background:

    • Distinguishing lymphoblastic from myeloblastic leukaemias is crucial, especially in adults where c-ALL antigen is often negative.
    • Immunofluorescence assays with antisera to surface membrane antigens detect small lymphoblast numbers in extramedullary sites or residual leukaemic cells.
    • Enzyme differences in purine metabolism exist between leukaemic blast cells, with Adenosine Deaminase (ADA) concentrations higher in T-cell acute lymphoblastic leukaemia (Thy-ALL).

    Purpose of the Study:

    • To review diagnostic assays for acute leukaemias, including Terminal deoxynucleotidyl transferase (TdT) and immunofluorescence.
    • To explore the role of Adenosine Deaminase (ADA) and its inhibition in T-cell acute lymphoblastic leukaemia (Thy-ALL).
    • To discuss the application of monoclonal antibodies in analysing leukaemic cell heterogeneity and potential therapeutic strategies.

    Main Methods:

    • Utilized Terminal deoxynucleotidyl transferase (TdT) assays for leukaemia classification.
    • Employed immunofluorescence assays with antisera to surface membrane antigens for leukaemic cell detection.
    • Analyzed enzyme concentrations, specifically Adenosine Deaminase (ADA), in leukaemic blast cells.
    • Reviewed the use of monoclonal antibodies for characterizing bone marrow stem cells and leukaemic cell lineages.

    Main Results:

    • TdT assays distinguish lymphoblastic from myeloblastic leukaemias.
    • Immunofluorescence detects small leukaemic cell populations in various sites.
    • Thy-ALL blasts exhibit higher ADA concentrations, though with overlap, and are uniquely sensitive to ADA inhibition by deoxycoformycin, leading to remissions in resistant cases.
    • Monoclonal antibodies reveal heterogeneity in Thy-ALL and delineate progenitor cell populations.

    Conclusions:

    • TdT and immunofluorescence are valuable tools in acute leukaemia diagnosis and monitoring.
    • Selective ADA inhibition with deoxycoformycin offers a promising therapeutic approach for Thy-ALL.
    • Monoclonal antibodies enhance understanding of leukaemic heterogeneity and offer potential for targeted therapies in transplantation and disease recurrence prevention.

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