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.
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http://dx.doi.org/10.1097/FPC.0000000000000072 | DOI Listing |
Blood Cells Mol Dis
December 2014
Hemocentro e Instituto Nacional de Ciência e Tecnologia do Sangue, Universidade de Campinas, São Paulo, Brazil. Electronic address:
Pyrimidine-5'-nucleotidase type I (P5'NI) deficiency is an autosomal recessive condition that causes nonspherocytic hemolytic anemia, characterized by marked basophilic stippling and pyrimidine nucleotide accumulation in erythrocytes. We herein present two African descendant patients, father and daughter, with P5'N deficiency, both born from first cousins. Investigation of the promoter polymorphism of the uridine diphospho glucuronosyl transferase 1A (UGT1A) gene revealed that the father was homozygous for the allele (TA7) and the daughter heterozygous (TA6/TA7).
View Article and Find Full Text PDFPharmacogenet Genomics
September 2014
aCancer Research Institute bDepartment of Internal Medicine, Seoul National University College of Medicine cClinical Research Institute, Seoul National University Hospital dDepartment of Genetic Epidemiology, SNP Genetics Inc. eFunctional Genome Institute, PDXen Biosystem Inc. fDepartment of Life Science, Sogang University, Seoul, Korea.
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.
Pharmacogenomics
July 2012
Department of Experimental & Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA.
Pharmacogenet Genomics
August 2009
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota 55905, USA.
Background: 5'-Nucleotidases play a critical role in nucleotide pool balance and in the metabolism of nucleoside analogs such as gemcitabine and cytosine arabinoside (AraC). We previously performed an expression array association study with gemcitabine and AraC cytotoxicity using 197 human lymphoblastoid cell lines. One gene that was significantly associated with gemcitabine cytotoxicity was a nucleotidase family member, NT5C3.
View Article and Find Full Text PDFDrug Metab Dispos
December 2008
Laboratoire de Cytologie Analytique, INSERM U590, Faculté de Médecine Rockefeller, 8, Avenue Rockefeller, 69008 Lyon, France.
mRNA expression levels of certain genes have shown predictive value for the outcome of cytarabine-treated AML-patients. We hypothesized that genetic variants play a role in the regulation of the transcription of these genes. We studied leukoblasts from 82 patients with acute myeloid leukemia and observed various extent and frequency of differential allelic expression in the CDA, DCK, NT5C2, NT5C3, and TP53 genes.
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