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Thymidine kinase 1 – A prognostic and diagnostic indicator in ALL and AML patients

Leukemia volume 21, pages 560–563 (2007)Cite this article

Acute leukemias are a collection of diseases represented by a predominance of undifferentiated or immature lymphoid (acute lymphoid leukemia (ALL)) or myeloid (acute myelogenous leukemia (AML)) precursors in bone marrow and peripheral blood. Malignant cells replace normal marrow cells and disrupt routine blood cell function, leading to death within weeks to months if left untreated. Chemotherapeutic advances have dramatically altered the management of patients with acute leukemias. Both ALL and AML patients can reasonably expect an extended disease-free survival period. Notwithstanding the improvements made in the treatment of these diseases, some patients remain at risk of relapse.1

The ability to monitor patient response to treatment would enhance disease management. The putative cancer marker, thymidine kinase (TK), has been shown to be elevated in the serum of patients with a variety of human malignancies.2 TK is a pyrimidine salvage pathway enzyme involved in DNA synthesis and repair. In the presence of adenosine triphosphate, TK catalyzes the conversion of thymidine to thymidine monophosphate (dTMP), dTMP is subsequently phosphorylated to its triphosphate analog (dTTP) by TK.3 TK is present in human cells in two major forms, TK1 and TK2. During the G1/S transition of normal cells, TK1 levels increase by 10- to 20-fold. TK1 levels remain elevated in the cell until M phase, at which time TK1 is rapidly degraded.4 The rate of degradation appears to change in a cell-cycle-dependent manner, resulting in the increased observed levels of TK1 activity. Cancer cells are known to have lost cell-cycle control of TK1, which leads to increased levels of TK1 in these cells and could possibly explain the elevations found in serum. TK2, the other major TK isozyme, is of mitochondrial origin and its levels are independent of the cell cycle and remain constant in both cancer cells and normal cells, as well as sera.5

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Acknowledgements

We thank KEM Baillie and JM Bridges for providing the serial blood samples from the ALL and AML patients. We also thank the Biological Carcinogenesis Branch for providing blood samples.

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Authors and Affiliations

  1. Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT, USA

    K L O'Neill, F Zhang, H Li, D G Fuja & B K Murray

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  1. K L O'Neill
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Correspondence to K L O'Neill.

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O'Neill, K., Zhang, F., Li, H. et al. Thymidine kinase 1 – A prognostic and diagnostic indicator in ALL and AML patients. Leukemia 21, 560–563 (2007). https://doi.org/10.1038/sj.leu.2404536

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