Correlation Engine 2.0
Clear Search sequence regions

  • antimetabolites (2)
  • ara c (8)
  • ara ctp (2)
  • deoxycytidine (2)
  • dose drug (1)
  • help (1)
  • humans (1)
  • intracellular (3)
  • myeloid leukemia (3)
  • patients (2)
  • reductases (2)
  • RRM1 (1)
  • RRM2 (1)
  • Sizes of these terms reflect their relevance to your search.

    The mainstay of acute myeloid leukemia chemotherapy is the nucleoside analog cytarabine (ara-C). Numerous studies suggest that the intracellular concentrations of the ara-C active metabolite, ara-CTP, vary widely among patients and, in turn, are associated with variability in clinical response to acute myeloid leukemia treatment. Thus, genetic variation in key genes in the ara-C metabolic pathway--specifically, deoxycytidine kinase (a rate-limiting activating enzyme), 5 nucleotidase, cytidine deaminase and deoxycytidylate deaminase (all three are inactivating enzymes), human equilibrative nucleoside transporter (ara-C uptake transporter) and ribonucleotide reductase (RRM1 and RRM2--enzymes regulating intracellular deoxycytidine triphosphate pools)--form the molecular basis of the interpatient variability observed in intracellular ara-CTP concentrations and response to ara-C. Understanding genetic variants in the key candidate genes involved in the metabolic activation of ara-C, as well as the pharmacodynamic targets of ara-C, will provide an opportunity to identify patients at an increased risk of adverse reactions or decreased likelihood of response, based upon their genetic profile, which in future could help in dose optimization to reduce drug toxicity without compromising efficacy. The pharmacogenetic studies on ara-C would also be equally applicable to other nucleoside analogs, such as gemcitabine, decitabine, clofarabine and so on, which are metabolized by the same pathway.


    Jatinder K Lamba. Genetic factors influencing cytarabine therapy. Pharmacogenomics. 2009 Oct;10(10):1657-74

    Expand section icon Mesh Tags

    Expand section icon Substances

    PMID: 19842938

    View Full Text