Genomic and transcriptomic profiling of resistant CEM/ADR-5000 and sensitive CCRF-CEM leukaemia cells for unravelling the full complexity of multi- factorial multidrug resistance
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Onat Kadioglu
- Jingming Cao
- Nadezda Kosyakova
- Kristin Mrasek
- Thomas Liehr
- Thomas Efferth
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000387325100001&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1038/srep36754
- Externe Identifier
- Clarivate Analytics Document Solution ID: EB4FK
- PubMed Identifier: 27824156
- ISSN
- 2045-2322
- Zeitschrift
- SCIENTIFIC REPORTS
- Artikelnummer
- ARTN 36754
- Datum der Veröffentlichung
- 2016
- Status
- Published
- Titel
- Genomic and transcriptomic profiling of resistant CEM/ADR-5000 and sensitive CCRF-CEM leukaemia cells for unravelling the full complexity of multi- factorial multidrug resistance
- Sub types
- Article
- Ausgabe der Zeitschrift
- 6
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Abstract
- <jats:title>Abstract</jats:title><jats:p>We systematically characterised multifactorial multidrug resistance (MDR) in CEM/ADR5000 cells, a doxorubicin-resistant sub-line derived from drug-sensitive, parental CCRF-CEM cells developed <jats:italic>in vitro</jats:italic>. RNA sequencing and network analyses (Ingenuity Pathway Analysis) were performed. Chromosomal aberrations were identified by array-comparative genomic hybridisation (aCGH) and multicolour fluorescence <jats:italic>in situ</jats:italic> hybridisation (mFISH). Fifteen ATP-binding cassette transporters and numerous new genes were overexpressed in CEM/ADR5000 cells. The basic karyotype in CCRF-CEM cells consisted of 47, XX, der(5)t(5;14) (q35.33;q32.3), del(9) (p14.1), +20. CEM/ADR5000 cells acquired additional aberrations, including X-chromosome loss, 4q and 14q deletion, chromosome 7 inversion, balanced and unbalanced two and three way translocations: t(3;10), der(3)t(3;13), der(5)t(18;5;14), t(10;16), der(18)t(7;18), der(18)t(21;18;5), der(21;21;18;5) and der(22)t(9;22). CCRF-CEM consisted of two and CEM/ADR5000 of five major sub-clones, indicating genetic tumor heterogeneity. Loss of 3q27.1 in CEM/ADR5000 caused down-regulation of <jats:italic>ABCC5</jats:italic> and <jats:italic>ABCF3</jats:italic> expression, Xq28 loss down-regulated <jats:italic>ABCD1</jats:italic> expression. <jats:italic>ABCB1</jats:italic>, the most well-known MDR gene, was 448-fold up-regulated due to 7q21.12 amplification. In addition to well-known drug resistance genes, numerous novel genes and genomic aberrations were identified. Transcriptomics and genetics in CEM/AD5000 cells unravelled a range of MDR mechanisms, which is much more complex than estimated thus far. This may have important implications for future treatment strategies.</jats:p>
- Autoren
- Onat Kadioglu
- Jingming Cao
- Nadezda Kosyakova
- Kristin Mrasek
- Thomas Liehr
- Thomas Efferth
- DOI
- 10.1038/srep36754
- eISSN
- 2045-2322
- Ausgabe der Veröffentlichung
- 1
- Zeitschrift
- Scientific Reports
- Sprache
- en
- Artikelnummer
- 36754
- Online publication date
- 2016
- Status
- Published online
- Herausgeber
- Springer Science and Business Media LLC
- Herausgeber URL
- http://dx.doi.org/10.1038/srep36754
- Datum der Datenerfassung
- 2023
- Titel
- Genomic and transcriptomic profiling of resistant CEM/ADR-5000 and sensitive CCRF-CEM leukaemia cells for unravelling the full complexity of multi-factorial multidrug resistance
- Ausgabe der Zeitschrift
- 6
Data source: Crossref
- Abstract
- We systematically characterised multifactorial multidrug resistance (MDR) in CEM/ADR5000 cells, a doxorubicin-resistant sub-line derived from drug-sensitive, parental CCRF-CEM cells developed in vitro. RNA sequencing and network analyses (Ingenuity Pathway Analysis) were performed. Chromosomal aberrations were identified by array-comparative genomic hybridisation (aCGH) and multicolour fluorescence in situ hybridisation (mFISH). Fifteen ATP-binding cassette transporters and numerous new genes were overexpressed in CEM/ADR5000 cells. The basic karyotype in CCRF-CEM cells consisted of 47, XX, der(5)t(5;14) (q35.33;q32.3), del(9) (p14.1), +20. CEM/ADR5000 cells acquired additional aberrations, including X-chromosome loss, 4q and 14q deletion, chromosome 7 inversion, balanced and unbalanced two and three way translocations: t(3;10), der(3)t(3;13), der(5)t(18;5;14), t(10;16), der(18)t(7;18), der(18)t(21;18;5), der(21;21;18;5) and der(22)t(9;22). CCRF-CEM consisted of two and CEM/ADR5000 of five major sub-clones, indicating genetic tumor heterogeneity. Loss of 3q27.1 in CEM/ADR5000 caused down-regulation of ABCC5 and ABCF3 expression, Xq28 loss down-regulated ABCD1 expression. ABCB1, the most well-known MDR gene, was 448-fold up-regulated due to 7q21.12 amplification. In addition to well-known drug resistance genes, numerous novel genes and genomic aberrations were identified. Transcriptomics and genetics in CEM/AD5000 cells unravelled a range of MDR mechanisms, which is much more complex than estimated thus far. This may have important implications for future treatment strategies.
- Addresses
- Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany.
- Autoren
- Onat Kadioglu
- Jingming Cao
- Nadezda Kosyakova
- Kristin Mrasek
- Thomas Liehr
- Thomas Efferth
- Thomas Efferth
- DOI
- 10.1038/srep36754
- eISSN
- 2045-2322
- Externe Identifier
- PubMed Identifier: 27824156
- PubMed Central ID: PMC5099876
- Open access
- true
- ISSN
- 2045-2322
- Zeitschrift
- Scientific reports
- Schlüsselwörter
- Humans
- Leukemia
- Translocation, Genetic
- Neoplasm Proteins
- In Situ Hybridization, Fluorescence
- Gene Expression Profiling
- Sequence Analysis, RNA
- Genomics
- DNA Repair
- Down-Regulation
- Drug Resistance, Neoplasm
- Genome
- Comparative Genomic Hybridization
- Transcriptome
- ATP Binding Cassette Transporter, Subfamily G, Member 2
- ATP Binding Cassette Transporter, Subfamily B
- Sprache
- eng
- Medium
- Electronic
- Online publication date
- 2016
- Open access status
- Open Access
- Paginierung
- 36754
- Datum der Veröffentlichung
- 2016
- Status
- Published
- Publisher licence
- CC BY
- Datum der Datenerfassung
- 2016
- Titel
- Genomic and transcriptomic profiling of resistant CEM/ADR-5000 and sensitive CCRF-CEM leukaemia cells for unravelling the full complexity of multi-factorial multidrug resistance.
- Sub types
- research-article
- Journal Article
- Ausgabe der Zeitschrift
- 6
Files
https://www.nature.com/articles/srep36754.pdf https://europepmc.org/articles/PMC5099876?pdf=render
Data source: Europe PubMed Central
- Abstract
- We systematically characterised multifactorial multidrug resistance (MDR) in CEM/ADR5000 cells, a doxorubicin-resistant sub-line derived from drug-sensitive, parental CCRF-CEM cells developed in vitro. RNA sequencing and network analyses (Ingenuity Pathway Analysis) were performed. Chromosomal aberrations were identified by array-comparative genomic hybridisation (aCGH) and multicolour fluorescence in situ hybridisation (mFISH). Fifteen ATP-binding cassette transporters and numerous new genes were overexpressed in CEM/ADR5000 cells. The basic karyotype in CCRF-CEM cells consisted of 47, XX, der(5)t(5;14) (q35.33;q32.3), del(9) (p14.1), +20. CEM/ADR5000 cells acquired additional aberrations, including X-chromosome loss, 4q and 14q deletion, chromosome 7 inversion, balanced and unbalanced two and three way translocations: t(3;10), der(3)t(3;13), der(5)t(18;5;14), t(10;16), der(18)t(7;18), der(18)t(21;18;5), der(21;21;18;5) and der(22)t(9;22). CCRF-CEM consisted of two and CEM/ADR5000 of five major sub-clones, indicating genetic tumor heterogeneity. Loss of 3q27.1 in CEM/ADR5000 caused down-regulation of ABCC5 and ABCF3 expression, Xq28 loss down-regulated ABCD1 expression. ABCB1, the most well-known MDR gene, was 448-fold up-regulated due to 7q21.12 amplification. In addition to well-known drug resistance genes, numerous novel genes and genomic aberrations were identified. Transcriptomics and genetics in CEM/AD5000 cells unravelled a range of MDR mechanisms, which is much more complex than estimated thus far. This may have important implications for future treatment strategies.
- Date of acceptance
- 2016
- Autoren
- Onat Kadioglu
- Jingming Cao
- Nadezda Kosyakova
- Kristin Mrasek
- Thomas Liehr
- Thomas Efferth
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/27824156
- DOI
- 10.1038/srep36754
- eISSN
- 2045-2322
- Externe Identifier
- PubMed Central ID: PMC5099876
- Zeitschrift
- Sci Rep
- Schlüsselwörter
- ATP Binding Cassette Transporter, Subfamily B
- ATP Binding Cassette Transporter, Subfamily G, Member 2
- Comparative Genomic Hybridization
- DNA Repair
- Down-Regulation
- Drug Resistance, Neoplasm
- Gene Expression Profiling
- Genome
- Genomics
- Humans
- In Situ Hybridization, Fluorescence
- Leukemia
- Neoplasm Proteins
- Sequence Analysis, RNA
- Transcriptome
- Translocation, Genetic
- Sprache
- eng
- Country
- England
- Paginierung
- 36754
- PII
- srep36754
- Datum der Veröffentlichung
- 2016
- Status
- Published online
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2018
- Titel
- Genomic and transcriptomic profiling of resistant CEM/ADR-5000 and sensitive CCRF-CEM leukaemia cells for unravelling the full complexity of multi-factorial multidrug resistance.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 6
Data source: PubMed
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