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Deoxyribonucleoside triphosphate accumulation by leukemic cells.

B S Mitchell, N L Edwards, C A Koller

    Blood
    |August 1, 1983
    PubMed
    Summary

    Leukemic cells can accumulate deoxyadenosine triphosphate (dATP) when exposed to deoxyadenosine. This finding supports deoxyribonucleosides as potential chemotherapeutic agents for certain leukemias.

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    Area of Science:

    • Biochemistry
    • Oncology
    • Pharmacology

    Background:

    • Deoxyribonucleoside toxicity in T lymphoblasts is linked to deoxyribonucleoside triphosphate accumulation.
    • Investigating deoxyribonucleotide accumulation in non-T-cell leukemias is crucial for understanding drug resistance and developing new therapies.

    Purpose of the Study:

    • To determine if non-T-cell origin leukemic cells can accumulate deoxyribonucleotides.
    • To assess the correlation between deoxyribonucleotide accumulation and purine metabolizing enzyme activities in these cells.

    Main Methods:

    • Culturing non-T, non-B acute lymphoblastic leukemia cells with deoxyadenosine and an adenosine deaminase inhibitor.
    • Measuring deoxyadenosine triphosphate (dATP) pools and enzyme activities (adenosine deaminase, purine nucleoside phosphorylase, ecto-5'-nucleotidase).
    • Administering 2'-deoxycoformycin to patients with acute lymphoblastic leukemia and monitoring plasma deoxyadenosine and lymphoblast dATP levels.

    Main Results:

    • Non-T, non-B acute lymphoblastic leukemia cells significantly increased dATP pools (over tenfold) when treated with deoxyadenosine and an adenosine deaminase inhibitor.
    • Some chronic lymphocytic leukemia and acute nonlymphoblastic leukemia cells also showed dATP elevations, but without a clear correlation to specific enzyme activities.
    • In vivo administration of 2'-deoxycoformycin mirrored in vitro findings, increasing plasma deoxyadenosine and lymphoblast dATP.

    Conclusions:

    • Certain leukemic cells possess the capability to accumulate deoxyribonucleotides, particularly dATP.
    • The accumulation of deoxyribonucleotides in leukemic cells suggests a potential therapeutic strategy.
    • In vitro studies with deoxyribonucleosides and enzyme inhibitors may inform the development of novel chemotherapy for leukemia.

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