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

Cheong, Hyun Suba,d; Koh, Youngilb; Ahn, Kwang-Sunge; Lee, Chansua; Shin, Hyoung Dood,f; Yoon, Sung-Sooa,b,c

doi: 10.1097/FPC.0000000000000072
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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 χ2 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.

Supplemental Digital Content is available in the text.

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

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (www.pharmacogeneticsandgenomics.com).

Correspondence to Sung-Soo Yoon, MD, Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehang-ro, Jongno-gu, Seoul 110-744, Korea Tel: +82 2 2072 3079; fax: +82 2 762 9662; e-mail: ssysmc@snu.ac.kr

Received February 20, 2014

Accepted May 26, 2014

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins