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

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...

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Autores principales: Komiyama, Tomoyoshi, Ogura, Atsushi, Hirokawa, Takatsugu, Zhijing, Miao, Kamiguchi, Hiroshi, Asai, Satomi, Miyachi, Hayato, Kobayashi, Hiroyuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5297647/
https://www.ncbi.nlm.nih.gov/pubmed/28025493
http://dx.doi.org/10.3390/ijms18010012
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author Komiyama, Tomoyoshi
Ogura, Atsushi
Hirokawa, Takatsugu
Zhijing, Miao
Kamiguchi, Hiroshi
Asai, Satomi
Miyachi, Hayato
Kobayashi, Hiroyuki
author_facet Komiyama, Tomoyoshi
Ogura, Atsushi
Hirokawa, Takatsugu
Zhijing, Miao
Kamiguchi, Hiroshi
Asai, Satomi
Miyachi, Hayato
Kobayashi, Hiroyuki
author_sort Komiyama, Tomoyoshi
collection PubMed
description 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.
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spelling pubmed-52976472017-02-10 Analysis to Estimate Genetic Variations in the Idarubicin-Resistant Derivative MOLT-3 Komiyama, Tomoyoshi Ogura, Atsushi Hirokawa, Takatsugu Zhijing, Miao Kamiguchi, Hiroshi Asai, Satomi Miyachi, Hayato Kobayashi, Hiroyuki Int J Mol Sci Article 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. MDPI 2016-12-22 /pmc/articles/PMC5297647/ /pubmed/28025493 http://dx.doi.org/10.3390/ijms18010012 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Komiyama, Tomoyoshi
Ogura, Atsushi
Hirokawa, Takatsugu
Zhijing, Miao
Kamiguchi, Hiroshi
Asai, Satomi
Miyachi, Hayato
Kobayashi, Hiroyuki
Analysis to Estimate Genetic Variations in the Idarubicin-Resistant Derivative MOLT-3
title Analysis to Estimate Genetic Variations in the Idarubicin-Resistant Derivative MOLT-3
title_full Analysis to Estimate Genetic Variations in the Idarubicin-Resistant Derivative MOLT-3
title_fullStr Analysis to Estimate Genetic Variations in the Idarubicin-Resistant Derivative MOLT-3
title_full_unstemmed Analysis to Estimate Genetic Variations in the Idarubicin-Resistant Derivative MOLT-3
title_short Analysis to Estimate Genetic Variations in the Idarubicin-Resistant Derivative MOLT-3
title_sort analysis to estimate genetic variations in the idarubicin-resistant derivative molt-3
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5297647/
https://www.ncbi.nlm.nih.gov/pubmed/28025493
http://dx.doi.org/10.3390/ijms18010012
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