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15.07.2016 | Original Article

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

verfasst von: Jeong-Hyun Kim, Chansu Lee, Hyun Sub Cheong, Youngil Koh, Kwang-Sung Ahn, Hyung-Lae Kim, Hyoung Doo Shin, Sung-Soo Yoon

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 3/2016

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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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Titel: SLC29A1 (ENT1) polymorphisms and outcome of complete remission in acute myeloid leukemia
verfasst von: Jeong-Hyun Kim
Chansu Lee
Hyun Sub Cheong
Youngil Koh
Kwang-Sung Ahn
Hyung-Lae Kim
Hyoung Doo Shin
Sung-Soo Yoon
Publikationsdatum: 15.07.2016
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 3/2016
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-016-3103-x

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

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Purpose

Methods

Results

Conclusions

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