## Replication Study: Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia <br> **Abstract** In 2015, as part of the Reproducibility Project: Cancer Biology, we published a Registered Report ([Fung et al., 2015][1]), that described how we intended to replicate selected experiments from the paper "Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia" ([Dawson et al., 2011][2]). Here we report the results of those experiments. We found that treatment of MLL-fusion leukaemia cells (MV4;11 cell line) with the BET bromodomain inhibitor I-BET151 resulted in selective growth inhibition that was not observed in leukaemia cells harboring a different oncogenic driver (K-562 cell line), similar to those reported in the original study (Figure 2A and Supplementary Figure 11A,B; [Dawson et al., 2011][3]). Further, I-BET151 resulted in a statistically significant decrease in *BCL2* expression in MV4;11 cells, but not K-562 cells, similar to the original study (Figure 3D; [Dawson et al., 2011][4]). We did not find a statistically significant difference in survival when testing I-BET151 efficacy in a disseminated xenograft MLL mouse model, whereas the original study reported an increase in survival in I-BET151 treated mice compared to vehicle control (Figure 4B,D; [Dawson et al., 2011][5]). Monitoring the extent of disease burden in this mouse model, we found I-BET151 treatment resulted in a lower median disease burden compared to vehicle control in all tissues analyzed, similar to the example reported in the original study (Supplementary Figure 16A; [Dawson et al., 2011][6]). Importantly, deviations in this replication attempt compared to the original study, such as a different conditioning regimen and a decreased I-BET151 dose, are factors that might have influenced the outcome. Finally, we report meta-analyses for each result. ---------- ## Contents <br> **Reports**: Read the [Replication Study][18], or view the [preprint versions][7] To reproduce the manuscript text run this in [R Studio][8] (note: downloads [R markdown file][9] directly from osf.io): library(httr) library(rmarkdown) GET("https://osf.io/cn9gy/?action=download", write_disk("Replication_Study_29.Rmd", overwrite = T)) render("Replication_Study_29.Rmd", output_format = "word_document") Also, explore the [Registered Report][10] and materials related to the Registered Report [here][11]. <br> **Experiments replicated**: Reproduce and explore the figures, analyses, data, and methods generated in this replication attempt. - [Evaluating the selective inhibition of a MLL-fusion leukemic cell line with I-BET151][12] - Replication of Figure 2A and Supplementary Figure 11A,B in Dawson et al., 2011. - [Analysis of *BCL2* gene expression following I-BET151 treatment][13] - Replication of Figure 3D in Dawson et al., 2011. - [Assessment of maximum tolerated dose of I-BET151 in xenograft MLL mouse model][14] and [Generation of disseminated xenograft MLL mouse model and testing of I-BET151 compound *in vivo*][15] - Replication of Figure 4B,D and Supplementary Figure 16A in Dawson et al., 2011. <br> **Meta-Analysis**: As a measure of evaluating reproducibility, a meta-analysis of each effect was performed. The forest plots, analyses, and data are available [here][16]. <br> Questions about the project can be directed to [contact+rpcb@cos.io][17]. ---------- [1]: https://elifesciences.org/content/4/e08997 [2]: http://www.nature.com/nature/journal/v478/n7370/full/nature10509.html [3]: http://www.nature.com/nature/journal/v478/n7370/full/nature10509.html [4]: http://www.nature.com/nature/journal/v478/n7370/full/nature10509.html [5]: http://www.nature.com/nature/journal/v478/n7370/full/nature10509.html [6]: http://www.nature.com/nature/journal/v478/n7370/full/nature10509.html [7]: https://osf.io/w9x9z/ [8]: https://www.rstudio.com [9]: https://osf.io/cn9gy/ [10]: https://elifesciences.org/content/4/e08997 [11]: https://osf.io/bdk6c/ [12]: https://osf.io/zm3j4/wiki/home/ [13]: https://osf.io/np6gq/wiki/home/ [14]: https://osf.io/juzmg/wiki/home/ [15]: https://osf.io/jakpw/wiki/home/ [16]: https://osf.io/vfp47/wiki/home/ [17]: mailto:contact+rpcb@cos.io [18]: https://elifesciences.org/articles/25306