NT5C3 polymorphisms and outcome of first induction chemotherapy in acute myeloid leukemia

Pharmacogenet Genomics. 2014 Sep;24(9):436-41. doi: 10.1097/FPC.0000000000000072.

Abstract

Aims: The cytosolic 5'-nucleotidase-III (NT5C3) is involved in the metabolism of the nucleoside analog, cytosine arabinose (AraC), and the expression level of NT5C3 is correlated with sensitivity to AraC in acute myeloid leukemia (AML) patients. The current study examined whether the NT5C3 polymorphisms could affect chemotherapy outcomes in 103 Korean AML patients.

Methods: Forty-seven single nucleotide polymorphisms in NT5C3 were genotyped using the Illumina GoldenGate genotyping assay. The genetic effects of the polymorphisms on the outcome of chemotherapy were analyzed using χ and logistic regression models.

Results: Although none of the NT5C3 polymorphisms was associated with a complete remission rate, a common single nucleotide polymorphism, rs3750117, showed a significant association with induction rate after the first course of chemotherapy (Pcorr=0.004 and odds ratio=11.28) in AML patients. In addition, NT5C3 expression levels were significantly increased in patients with risk allele homozygote.

Conclusions: The data suggest that genotyping the NT5C3 polymorphism may have the potential to identify patients more likely to respond to AraC-based chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5'-Nucleotidase / genetics*
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Cytarabine / therapeutic use*
  • Female
  • Genetic Association Studies
  • Genetic Variation
  • Genotype
  • Glycoproteins / genetics*
  • Humans
  • Induction Chemotherapy / methods*
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / genetics
  • Male
  • Polymorphism, Single Nucleotide
  • Republic of Korea
  • Treatment Outcome

Substances

  • Antimetabolites, Antineoplastic
  • Glycoproteins
  • Cytarabine
  • 5'-Nucleotidase
  • NT5C3A protein, human