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Int. J. Mol. Sci. 2017, 18(1), 12; doi:10.3390/ijms18010012

Analysis to Estimate Genetic Variations in the Idarubicin-Resistant Derivative MOLT-3

1
Department of Clinical Pharmacology, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan
2
Nagahama Institute of Bio-Science and Technology, Nagahama, Shiga 526-0829, Japan
3
The National Institute of Advanced Industrial Science and Technology (AIST), Tokyo Waterfront Bio-IT Research Building 2-4-7 Aomi, Koto-ku, Tokyo 135-0064, Japan
4
Support Center for Medical Research and Education, Tokai University, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan
5
Department of Laboratory Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan
*
Authors to whom correspondence should be addressed.
Academic Editor: Emil Alexov
Received: 3 October 2016 / Revised: 6 December 2016 / Accepted: 13 December 2016 / Published: 22 December 2016
(This article belongs to the Collection Human Single Nucleotide Polymorphisms and Disease Diagnostics)
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Abstract

Gene alterations are a well-established mechanism leading to drug resistance in acute leukemia cells. A full understanding of the mechanisms of drug resistance in these cells will facilitate more effective chemotherapy. In this study, we investigated the mechanism(s) of drug resistance in the human acute leukemia cell line MOLT-3 and its idarubicin-resistant derivative MOLT-3/IDR through complete mitochondrial and nuclear DNA analyses. We identified genetic differences between these two cell lines. The ND3 mutation site (p.Thr61Ile) in the mitochondrial DNA sequence was unique to MOLT-3/IDR cells. Moreover, we identified five candidate genes harboring genetic alterations, including GALNT2, via CGH array analysis. Sequencing of the GALNT2 exon revealed a G1716K mutation present within the stop codon in MOLT-3/IDR cells but absent from MOLT-3 cells. This mutation led to an additional 18 amino acids in the protein encoded by GALNT2. Using real-time PCR, we determined an expression value for this gene of 0.35. Protein structure predictions confirmed a structural change in GALNT2 in MOLT-3/IDR cells that corresponded to the site of the mutation. We speculate that this mutation may be related to idarubicin resistance. View Full-Text
Keywords: leukemia; MOLT-3; GALNT2 gene; gene polymorphism; mitochondrial DNA; CGH array; genetic variations; idarubicin (IDR) leukemia; MOLT-3; GALNT2 gene; gene polymorphism; mitochondrial DNA; CGH array; genetic variations; idarubicin (IDR)
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Komiyama, T.; Ogura, A.; Hirokawa, T.; Zhijing, M.; Kamiguchi, H.; Asai, S.; Miyachi, H.; Kobayashi, H. Analysis to Estimate Genetic Variations in the Idarubicin-Resistant Derivative MOLT-3. Int. J. Mol. Sci. 2017, 18, 12.

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