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Phenotypic heterogeneity in lymphoblastic cell lines.

L J Smith, E A McCulloch

    Journal of Cellular Physiology
    |May 1, 1986
    PubMed
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    Leukemic cell lines can exhibit markers from different cell types, a phenomenon known as lineage infidelity. Clonal selection reveals diverse subclones with unique marker expressions, suggesting plasticity in leukemia cell phenotypes.

    Area of Science:

    • Immunology
    • Hematology
    • Cell Biology

    Background:

    • Leukemic cell lines are crucial models for studying leukemia.
    • Understanding cell surface markers aids in leukemia classification and diagnosis.
    • Lineage infidelity, the expression of markers from unrelated lineages, is observed in some cancers.

    Purpose of the Study:

    • To investigate the expression of lineage and differentiation antigens in lymphoblastic leukemia cell lines.
    • To explore phenotypic heterogeneity and the emergence of variant subclones.
    • To assess the effect of 5-azacytidine on marker expression in leukemia cell lines.

    Main Methods:

    • Culturing of T-cell and B-cell lymphoblastic leukemia lines.
    • Immunophenotyping using a panel of monoclonal antibodies.

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  • Clonal selection and subclone analysis.
  • Treatment with 5-azacytidine (5-aza) and subsequent marker expression analysis.

    • Main Results:

    • Five of six cell lines displayed granulopoietic lineage markers, with variable expression during culture.
    • MOLT-3 cell line showed significant phenotypic heterogeneity upon clonal selection.
    • Subclones expressed novel markers not present in the parent clone, often with reproducible kinetics.
    • 5-azacytidine promoted granulopoietic antigen expression but inhibited other novel markers in subclones.

    Conclusions:

    • Lineage infidelity may be a characteristic of leukemic lymphoblasts.
    • Phenotypically variant subclones expressing lineage infidelity can be readily generated through clonal selection.
    • The drug 5-azacytidine has differential effects on the expression of various lineage-associated markers in leukemia subclones.