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Genes 2018, 9(8), 390; https://doi.org/10.3390/genes9080390

Analysis of Candidate Idarubicin Drug Resistance Genes in MOLT-3 Cells Using Exome Nuclear DNA

1
Department of Clinical Pharmacology, Tokai University School of Medicine, Kanagawa 259-1193, Japan
2
Nagahama Institute of Bio-Science and Technology, Shiga 526-0829, Japan
3
Support Center for Medical Research and Education, Tokai University, Kanagawa 259-1193, Japan
*
Authors to whom correspondence should be addressed.
Received: 18 May 2018 / Revised: 13 July 2018 / Accepted: 16 July 2018 / Published: 1 August 2018
(This article belongs to the Section Molecular Genetics and Genomics)
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Abstract

Various gene alterations related to acute leukemia are reported to be involved in drug resistance. We investigated idarubicin (IDR) resistance using exome nuclear DNA analyses of the human acute leukemia cell line MOLT-3 and the derived IDR-resistant cell line MOLT-3/IDR. We detected mutations in MOLT-3/IDR and MOLT-3 using both Genome Analysis Toolkit (GATK) and SnpEff program. We found 8839 genes with specific mutations in MOLT-3/IDR and 1162 genes with accompanying amino acid mutations. The 1162 genes were identified by exome analysis of polymerase-related genes using Kyoto Encyclopedia of Genes and Genomes (KEGG) and, among these, we identified genes with amino acid changes. In resistant strains, LIG and helicase plurality genes showed amino-acid-related changes. An amino acid mutation was also confirmed in polymerase-associated genes. Gene ontology (GO) enrichment testing was performed, and lipid-related genes were selected from the results. Fluorescent activated cell sorting (FACS) was used to determine whether IDR permeability was significantly different in MOLT-3/IDR and MOLT-3. The results showed that an IDR concentration of 0.5 μg/mL resulted in slow permeability in MOLT-3/IDR. This slow IDR permeability may be due to the effects of amino acid changes in polymerase- and lipid-associated genes. View Full-Text
Keywords: leukemia; MOLT-3; gene polymorphism; genetic variations; idarubicin; drug resistance leukemia; MOLT-3; gene polymorphism; genetic variations; idarubicin; drug resistance
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Komiyama, T.; Ogura, A.; Kajiwara, T.; Okada, Y.; Kobayashi, H. Analysis of Candidate Idarubicin Drug Resistance Genes in MOLT-3 Cells Using Exome Nuclear DNA. Genes 2018, 9, 390.

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