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SLC29A1 (ENT1) polymorphisms and outcome of complete remission in acute myeloid leukemia

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Abstract

Purpose

The solute carrier family 29 (equilibrative nucleoside transporter), member 1 (SLC29A1) is known to be involved in the transportation and resistance of the nucleoside analog cytosine arabinoside (AraC), one of the most effective drugs in the treatment of acute myeloid leukemia (AML).

Methods

In vitro functional analysis in AML cells and genetic association study were performed.

Results

Our functional analysis of SLC29A1 on anticancer effects of AraC showed that cytotoxic effects of AraC in AML cell lines were decreased by the reduction of SLC29A1 expression (P < 0.05). To investigate whether SLC29A1 polymorphisms could affect the achievement of complete remission (CR) in AML, we genotyped a total of six common single nucleotide polymorphisms on SLC29A1 in 103 AML patients, including 17 successes and 86 failures in CR. As a result, rs3734703 in 3’-untranslated region was significantly associated with CR even after correction for multiple testing (Fisher’s exact test, P = 0.008; P corr = 0.04). A haplotype, ht3 (A–G–G–T–C–A; frequency = 0.294 in success group; frequency = 0.120 in failure group), also revealed a significant association with CR (P = 0.01; simulated P sim = 0.02).

Conclusions

Although further replication in larger subjects and further functional evaluations are required, our results suggest the contribution of SLC29A1 to cytotoxic effects of AraC. In addition, genetic variations of SLC29A1 could be a potential marker for the achievement of CR of cancers of white blood cells including AML.

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Funding

This study was supported by Grant 03-2010-0080 from the SNUH Research Fund; the grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (Grant number: HI14C2399); the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (2011-0008846).

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Author notes

    Authors and Affiliations

    1. Research Institute for Basic Science, Sogang University, Seoul, Republic of Korea

      Jeong-Hyun Kim & Hyoung Doo Shin

    2. Cancer Research Institute, Seoul National University Hospital, Seoul, Republic of Korea

      Chansu Lee, Hyun Sub Cheong & Sung-Soo Yoon

    3. Department of Genetic Epidemiology, SNP Genetics Inc., Seoul, Republic of Korea

      Hyun Sub Cheong & Hyoung Doo Shin

    4. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea

      Youngil Koh & Sung-Soo Yoon

    5. Functional Genome Institute, PDXen Biosystem Inc., Seoul, Republic of Korea

      Kwang-Sung Ahn

    6. Department of Biochemistry, School of Medicine, Ewha Womans University, Seoul, Republic of Korea

      Hyung-Lae Kim

    7. Department of Life Science, Sogang University, Seoul, Republic of Korea

      Hyoung Doo Shin

    8. Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea

      Sung-Soo Yoon

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    1. Jeong-Hyun Kim
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    Correspondence to Sung-Soo Yoon.

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    Research involving human participants

    All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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    Informed consent was obtained from all individual participants included in the study.

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    Jeong-Hyun Kim and Chansu Lee have contributed equally to this work.

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    Kim, JH., Lee, C., Cheong, H.S. et al. SLC29A1 (ENT1) polymorphisms and outcome of complete remission in acute myeloid leukemia. Cancer Chemother Pharmacol 78, 533–540 (2016). https://doi.org/10.1007/s00280-016-3103-x

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    • DOI: https://doi.org/10.1007/s00280-016-3103-x

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