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## Replication Study: BET bromodomain inhibition as a therapeutic strategy to target c-Myc <br> **Abstract** In 2015, as part of the [Reproducibility Project: Cancer Biology][1], we published a Registered Report ([Kandela et al., 2015][2]), that described how we intended to replicate selected experiments from the paper "BET bromodomain inhibition as a therapeutic strategy to target c-Myc" ([Delmore et al., 2011][3]). Here we report the results of those experiments. We found that treatment of human multiple myeloma (MM) cells with the small-molecular inhibitor of BET bromodomains, (+)-JQ1, selectively downregulated _MYC_ transcription, which is similar to what was reported in the original study (Figure 3B; [Delmore et al., 2011][4]). Efficacy of (+)-JQ1 was evaluated in an orthotopically xenografted model of MM. Overall survival was increased in (+)-JQ1 treated mice compared to vehicle control, similar to the original study (Figure 7E; [Delmore et al., 2011][5]). Tumor burden, as determined by bioluminescence, was decreased in (+)-JQ1 treated mice compared to vehicle control; however, while the effect was in the same direction as the original study (Figure 7C-D; [Delmore et al., 2011][6]), it was not statistically significant. The opportunity to detect a statistically significant difference was limited though, due to the higher rate of early death in the control group, and increased overall survival in (+)-JQ1 treated mice, before the pre-specified tumor burden analysis endpoint. Additionally, we evaluated the (-)-JQ1 enantiomer that is structurally incapable of inhibiting BET bromodomains, which resulted in a minimal impact on MYC transcription, but did not result in a statistically significant difference in tumor burden or survival distributions compared to treatment with (+)-JQ1. Finally, we report meta-analyses for each result. ---------- ### Contents **Reports:** Read the [Replication Study][7], or view the [preprint versions][8]. To reproduce the Replication Study manuscript text run this in [R Studio][9] (note: downloads [R markdown file][10] directly from osf.io): library(httr) library(rmarkdown) GET("https://osf.io/sgru9/?action=download", write_disk("Replication_Study_19.Rmd", overwrite = T)) render("Replication_Study_19.Rmd", output_format = "word_document") <br> Also, explore the [Registered Report][11] and materials related to the Registered Report [here][12]. <br> **Experiments replicated:** Reproduce and explore the figures, analyses, data, and methods generated in this replication attempt. - [Evaluation of MYC expression in JQ1-treated MM.1S-luc cells][13] - Replication of Figure 3B in Delmore et al., 2011. - [Testing the efficacy of JQ1 treatment in mice harboring bioluminescent MM lesions][14] - Replication of Figures 7C, 7D, and 7E in Delmore et al., 2011. <br> **Meta-analyses:** As a measure of evaluating reproducibility a meta-analysis of each effect was performed. The forest plots, analyses, and data are available [here][15]. <br> Questions about the project can be directed to [contact+rpcb@cos.io][16]. [1]: https://osf.io/e81xl/wiki/home/ [2]: https://elifesciences.org/content/4/e07072 [3]: http://www.cell.com/cell/abstract/S0092-8674%2811%2900943-3?_returnURL=http://linkinghub.elsevier.com/retrieve/pii/S0092867411009433?showall=true [4]: http://www.cell.com/cell/abstract/S0092-8674%2811%2900943-3?_returnURL=http://linkinghub.elsevier.com/retrieve/pii/S0092867411009433?showall=true [5]: http://www.cell.com/cell/abstract/S0092-8674%2811%2900943-3?_returnURL=http://linkinghub.elsevier.com/retrieve/pii/S0092867411009433?showall=true [6]: http://www.cell.com/cell/abstract/S0092-8674%2811%2900943-3?_returnURL=http://linkinghub.elsevier.com/retrieve/pii/S0092867411009433?showall=true [7]: http://dx.doi.org/10.7554/eLife.21253 [8]: https://osf.io/2u4nh/ [9]: https://www.rstudio.com [10]: https://osf.io/sgru9/ [11]: https://elifesciences.org/content/4/e07072 [12]: https://osf.io/bjrpc/wiki/home/ [13]: https://osf.io/9swnx/wiki/home/ [14]: https://osf.io/pnvtd/wiki/home/ [15]: https://osf.io/9snja/wiki/home/ [16]: mailto:contact+rpcb@cos.io
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