BRD4-Regulated Molecular Targets in Mantle Cell Lymphoma : Insights into Targeted Therapeutic Approach
Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved..
BACKGROUND: Since bromodomain-containing protein 4 (BRD4) facilitates the transcription of genes important for neoplastic cells in a cancer-type specific manner, BRD4-regulated molecules may also include therapeutic targets for mantle cell lymphoma (MCL), a treatment-refractory subtype of malignant lymphoma.
MATERIALS AND METHODS: In order to uncover direct BRD4-regulated targets in MCL, we performed integrated analysis using the pathway database and the results of both gene-expression profiling and chromatin immunoprecipitation with parallel sequencing for BRD4.
RESULTS: Treatment with BRD4 inhibitor I-BET151 exerted a dose-dependent inhibitory effect on cell proliferation in MCL cell lines. BRD4 was found to directly regulate series of genes involved in the B-cell receptor (BCR) signaling pathway, including B-cell linker (BLNK), paired box 5 (PAX5), and IKAROS family zinc finger 3 (IKZF3), and several oncogenes, such as MYB. Indeed, the combinatory inhibition of BCR pathway and IKZF showed an additive antitumor effect.
CONCLUSION: Concomitant targeting multiple BRD4-regulated molecules may constitute a rational therapeutic strategy for MCL.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:17 |
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| Enthalten in: |
Cancer genomics & proteomics - 17(2020), 1 vom: 28. Jan., Seite 77-89 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Tsukamoto, Taku [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 02.06.2020 Date Revised 02.06.2020 published: Print Citation Status MEDLINE |
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| doi: |
10.21873/cgp.20169 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM304825670 |
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| 500 | |a Date Revised 02.06.2020 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved. | ||
| 520 | |a BACKGROUND: Since bromodomain-containing protein 4 (BRD4) facilitates the transcription of genes important for neoplastic cells in a cancer-type specific manner, BRD4-regulated molecules may also include therapeutic targets for mantle cell lymphoma (MCL), a treatment-refractory subtype of malignant lymphoma | ||
| 520 | |a MATERIALS AND METHODS: In order to uncover direct BRD4-regulated targets in MCL, we performed integrated analysis using the pathway database and the results of both gene-expression profiling and chromatin immunoprecipitation with parallel sequencing for BRD4 | ||
| 520 | |a RESULTS: Treatment with BRD4 inhibitor I-BET151 exerted a dose-dependent inhibitory effect on cell proliferation in MCL cell lines. BRD4 was found to directly regulate series of genes involved in the B-cell receptor (BCR) signaling pathway, including B-cell linker (BLNK), paired box 5 (PAX5), and IKAROS family zinc finger 3 (IKZF3), and several oncogenes, such as MYB. Indeed, the combinatory inhibition of BCR pathway and IKZF showed an additive antitumor effect | ||
| 520 | |a CONCLUSION: Concomitant targeting multiple BRD4-regulated molecules may constitute a rational therapeutic strategy for MCL | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Sato, Ryuichi |e verfasserin |4 aut | |
| 700 | 1 | |a Kanai, Akinori |e verfasserin |4 aut | |
| 700 | 1 | |a Nakano, Masakazu |e verfasserin |4 aut | |
| 700 | 1 | |a Chinen, Yoshiaki |e verfasserin |4 aut | |
| 700 | 1 | |a Maegawa-Matsui, Saori |e verfasserin |4 aut | |
| 700 | 1 | |a Matsumura-Kimoto, Yayoi |e verfasserin |4 aut | |
| 700 | 1 | |a Takimoto-Shimomura, Tomoko |e verfasserin |4 aut | |
| 700 | 1 | |a Mizuno, Yoshimi |e verfasserin |4 aut | |
| 700 | 1 | |a Kuwahara-Ota, Saeko |e verfasserin |4 aut | |
| 700 | 1 | |a Kawaji, Yuka |e verfasserin |4 aut | |
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| 700 | 1 | |a Inaba, Toshiya |e verfasserin |4 aut | |
| 700 | 1 | |a Tashiro, Kei |e verfasserin |4 aut | |
| 700 | 1 | |a Morishita, Kazuhiro |e verfasserin |4 aut | |
| 700 | 1 | |a Kuroda, Junya |e verfasserin |4 aut | |
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