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## Registered report: Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukemia <br> **Abstract** The [Reproducibility Project: Cancer Biology][1] 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][2] ([Errington et al., 2014][3]). 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][4]). 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][5] and [Science Exchange][6] and the results of the replications will be published in [*eLife*][7]. ---------- ### Contents This component contains additional materials relating to the Registered Report for Study 29: Dawson et al., 2011 (*Nature*). The published Registered Report can be found [here][8]. **Registered Report Initial Draft**: - This document represents the first draft of the selected experimental protocols. It contains the information that the Core team, with help from scientist volunteers, was able to glean from the original publication and its supplemental materials before the original authors were contacted for their input. - [Study 29 Registered Report Initial Draft][9] **Power Calculations**: - These documents contain details about how power calculations were performed, and include spreadsheets documenting statistical tests as well as any PRISM files, R scripts or additional materials used. - [Study 29 Power Calculations][10] - [Study 29 Figure 3D data estimation][11] - [Study 29 Figure 4B Kaplan-Meier.pzf][12] - [Study 29 Protocol 5 Figure 4B sample size calculation][13] [1]: https://osf.io/e81xl/wiki/home/ [2]: https://osf.io/e81xl/wiki/studies/ [3]: https://elifesciences.org/content/3/e04333 [4]: http://www.nature.com/nature/journal/v478/n7370/full/nature10509.html [5]: https://cos.io/ [6]: https://www.scienceexchange.com/ [7]: https://elifesciences.org/ [8]: http://elifesciences.org/content/4/e08997 [9]: https://osf.io/zyf43/ [10]: https://osf.io/uymqv/ [11]: https://osf.io/t43bw/ [12]: https://osf.io/mu5bg/ [13]: https://osf.io/pnb42/
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