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DNA ligases in human leukemia.

J C David, R Zittoun, T Bassez

    Leukemia Research
    |January 1, 1985
    PubMed
    Summary
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    DNA ligase activity differs significantly across leukemia types. Acute lymphoblastic leukemia (ALL) shows low or no DNA ligase, unlike acute myeloblastic leukemia (AML) and chronic leukemias, which exhibit higher activity.

    Area of Science:

    • Molecular Biology
    • Hematology
    • Oncology

    Background:

    • DNA ligase plays a crucial role in DNA replication and repair.
    • Leukemias are characterized by abnormal proliferation of blood cells.
    • Understanding enzyme activity in leukemic cells can offer diagnostic and prognostic insights.

    Purpose of the Study:

    • To investigate DNA ligase activity in various types of leukemia.
    • To compare DNA ligase levels with Terminal deoxynucleotidyl transferase (TdT) in leukemic cells.
    • To explore the correlation between DNA ligase activity and cell proliferation in acute myeloblastic leukemia (AML).

    Main Methods:

    • Partial purification of DNA ligase using sucrose gradient and phosphocellulose chromatography.
    • Assay of DNA ligase activity in peripheral white blood and bone marrow cells from nearly 100 leukemia patients.

    Related Experiment Videos

  • Parallel testing of Terminal deoxynucleotidyl transferase (TdT) activity.
  • Measurement of S phase fraction using 3H-thymidine autoradiography and flow cytometry.

    • Main Results:

    • DNA ligase in AML cells exhibited similar properties to normal lymphocytes.
    • Acute lymphoblastic leukemias (ALL) showed undetectable or low DNA ligase activity, inversely correlated with TdT levels.
    • Acute myeloblastic leukemia (AML) and chronic myelocytic leukemia (CML) displayed significantly higher DNA ligase activity.
    • Higher DNA ligase activity in AML correlated with more differentiated subtypes and increased S phase fraction.

    Conclusions:

    • DNA ligase activity serves as a potential biomarker differentiating leukemia subtypes.
    • The inverse relationship between DNA ligase and TdT in ALL suggests distinct cellular mechanisms.
    • Elevated DNA ligase in AML and CML may relate to increased DNA replication and repair demands in these malignancies.