Registered report: Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukemia
The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of selected experiments from a number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012, w...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2015-09-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/08997 |
| _version_ | 1797997471657361408 |
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| author | Juan José Fung Alan Kosaka Xiaochuan Shan Gwenn Danet-Desnoyers Michael Gormally Kate Owen Reproducibility Project: Cancer Biology |
| author_facet | Juan José Fung Alan Kosaka Xiaochuan Shan Gwenn Danet-Desnoyers Michael Gormally Kate Owen Reproducibility Project: Cancer Biology |
| author_sort | Juan José Fung |
| collection | DOAJ |
| description | The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of selected experiments from a number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012, were selected on the basis of citations and Altmetric scores (Errington et al., 2014). This Registered report describes the proposed replication plan of key experiments from ‘Inhibition of bromodomain and extra terminal (BET) recruitment to chromatin as an effective treatment for mixed-lineage leukemia (MLL)-fusion leukemia’ by Dawson and colleagues, published in Nature in 2011 (Dawson et al., 2011). The experiments to be replicated are those reported in Figures 2A, 3D, 4B, 4D and Supplementary Figures 11A-B and 16A. In this study, BET proteins were demonstrated as potential therapeutic targets for modulating aberrant gene expression programs associated with MLL-fusion leukemia. In Figure 2A, the BET bromodomain inhibitor I-BET151 was reported to suppress growth of cells harboring MLL-fusions compared to those with alternate oncogenic drivers. In Figure 3D, treatment of MLL-fusion leukemia cells with I-BET151 resulted in transcriptional suppression of the anti-apoptotic gene BCL2. Figures 4B and 4D tested the therapeutic efficacy of I-BET151 in vivo using mice injected with human MLL-fusion leukemia cells and evaluated disease progression following I-BET151 treatment. The Reproducibility Project: Cancer Biology is a collaboration between the Center for Open Science and Science Exchange and the results of the replications will be published in eLife. |
| first_indexed | 2024-04-11T10:33:35Z |
| format | Article |
| id | doaj.art-4d0c8be0eaf9468bb6f9d45c14d1e5eb |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T10:33:35Z |
| publishDate | 2015-09-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-4d0c8be0eaf9468bb6f9d45c14d1e5eb2022-12-22T04:29:21ZengeLife Sciences Publications LtdeLife2050-084X2015-09-01410.7554/eLife.08997Registered report: Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukemiaJuan José Fung0Alan Kosaka1Xiaochuan Shan2Gwenn Danet-Desnoyers3Michael Gormally4Kate Owen5Reproducibility Project: Cancer BiologyProNovus Bioscience, Mountain View, CaliforniaProNovus Bioscience, Mountain View, CaliforniaStem Cell and Xenograft Core, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PennsylvaniaStem Cell and Xenograft Core, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PennsylvaniaUniversity of Cambridge, Cambridge, United KingdomUniversity of Virginia, Charlottesville, VirginiaThe Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of selected experiments from a number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012, were selected on the basis of citations and Altmetric scores (Errington et al., 2014). This Registered report describes the proposed replication plan of key experiments from ‘Inhibition of bromodomain and extra terminal (BET) recruitment to chromatin as an effective treatment for mixed-lineage leukemia (MLL)-fusion leukemia’ by Dawson and colleagues, published in Nature in 2011 (Dawson et al., 2011). The experiments to be replicated are those reported in Figures 2A, 3D, 4B, 4D and Supplementary Figures 11A-B and 16A. In this study, BET proteins were demonstrated as potential therapeutic targets for modulating aberrant gene expression programs associated with MLL-fusion leukemia. In Figure 2A, the BET bromodomain inhibitor I-BET151 was reported to suppress growth of cells harboring MLL-fusions compared to those with alternate oncogenic drivers. In Figure 3D, treatment of MLL-fusion leukemia cells with I-BET151 resulted in transcriptional suppression of the anti-apoptotic gene BCL2. Figures 4B and 4D tested the therapeutic efficacy of I-BET151 in vivo using mice injected with human MLL-fusion leukemia cells and evaluated disease progression following I-BET151 treatment. The Reproducibility Project: Cancer Biology is a collaboration between the Center for Open Science and Science Exchange and the results of the replications will be published in eLife.https://elifesciences.org/articles/08997Reproducibility Project: Cancer Biologymethodologybromodomain inhibitorleukemia |
| spellingShingle | Juan José Fung Alan Kosaka Xiaochuan Shan Gwenn Danet-Desnoyers Michael Gormally Kate Owen Reproducibility Project: Cancer Biology Registered report: Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukemia eLife Reproducibility Project: Cancer Biology methodology bromodomain inhibitor leukemia |
| title | Registered report: Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukemia |
| title_full | Registered report: Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukemia |
| title_fullStr | Registered report: Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukemia |
| title_full_unstemmed | Registered report: Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukemia |
| title_short | Registered report: Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukemia |
| title_sort | registered report inhibition of bet recruitment to chromatin as an effective treatment for mll fusion leukemia |
| topic | Reproducibility Project: Cancer Biology methodology bromodomain inhibitor leukemia |
| url | https://elifesciences.org/articles/08997 |
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