{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T08:09:06Z","timestamp":1772266146090,"version":"3.50.1"},"reference-count":54,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2017,6,27]],"date-time":"2017-06-27T00:00:00Z","timestamp":1498521600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,6,27]],"date-time":"2017-06-27T00:00:00Z","timestamp":1498521600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,6,27]],"date-time":"2017-06-27T00:00:00Z","timestamp":1498521600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009827","name":"Laura and John Arnold Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009827","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>In 2015, as part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Fung et al., 2015), 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). Here, we report the results of those experiments. We found treatment of MLL-fusion leukaemia cells (MV4;11 cell line) with the BET bromodomain inhibitor I-BET151 resulted in selective growth inhibition, whereas treatment of leukaemia cells harboring a different oncogenic driver (K-562 cell line) did not result in selective growth inhibition; this is similar to the findings reported in the original study (Figure 2A and Supplementary Figure 11A,B; Dawson et al., 2011). Further, I-BET151 resulted in a statistically significant decrease in BCL2 expression in MV4;11 cells, but not in K-562 cells; again this is similar to the findings reported in the original study (Figure 3D; Dawson et al., 2011). 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 increased survival in I-BET151 treated mice compared to vehicle control (Figure 4B,D; Dawson et al., 2011). Differences between the original study and this replication attempt, such as different conditioning regimens and I-BET151 doses, are factors that might have influenced the outcome. We also 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). Finally, we report meta-analyses for each result.<\/jats:p>","DOI":"10.7554\/elife.25306","type":"journal-article","created":{"date-parts":[[2017,6,26]],"date-time":"2017-06-26T20:01:00Z","timestamp":1498507260000},"source":"Crossref","is-referenced-by-count":15,"title":["Replication Study: Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia"],"prefix":"10.7554","volume":"6","author":[{"given":"Xiaochuan","family":"Shan","sequence":"first","affiliation":[{"name":"University of Pennsylvania, Perelman School of Medicine, Stem Cell and Xenograft Core, Philadelphia, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan Jose","family":"Fung","sequence":"additional","affiliation":[{"name":"ProNovus Bioscience, LLC, Mountain View, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan","family":"Kosaka","sequence":"additional","affiliation":[{"name":"ProNovus Bioscience, LLC, Mountain View, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gwenn","family":"Danet-Desnoyers","sequence":"additional","affiliation":[{"name":"University of Pennsylvania, Perelman School of Medicine, Stem Cell and Xenograft Core, Philadelphia, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Reproducibility Project: Cancer Biology","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"4374","published-online":{"date-parts":[[2017,6,27]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"e196","DOI":"10.1016\/S2352-3026(16)00021-1","article-title":"Bromodomain inhibitor OTX015 in patients with lymphoma or multiple myeloma: a dose-escalation, open-label, pharmacokinetic, phase 1 study","volume":"3","author":"Amorim","year":"2016","journal-title":"The Lancet Haematology"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1158\/1541-7786.MCR-15-0472","article-title":"BET bromodomain inhibitors enhance efficacy and disrupt resistance to AR antagonists in the treatment of Prostate Cancer","volume":"14","author":"Asangani","year":"2016","journal-title":"Molecular Cancer Research"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"1018","DOI":"10.1158\/1535-7163.MCT-15-0567","article-title":"The Bromodomain BET Inhibitor JQ1 suppresses tumor angiogenesis in models of Childhood Sarcoma","volume":"15","author":"Bid","year":"2016","journal-title":"Molecular Cancer Therapeutics"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1177\/2040620715576662","article-title":"Inhibition of bromodomain and extra-terminal proteins (BET) as a potential therapeutic approach in haematological malignancies: emerging preclinical and clinical evidence","volume":"6","author":"Chaidos","year":"2015","journal-title":"Therapeutic Advances in Hematology"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"1974","DOI":"10.1101\/gad.226613.113","article-title":"Cancer-associated IDH2 mutants drive an acute myeloid leukemia that is susceptible to Brd4 inhibition","volume":"27","author":"Chen","year":"2013","journal-title":"Genes & Development"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1038\/509282a","article-title":"Policy: nih to balance sex in cell and animal studies","volume":"509","author":"Clayton","year":"2014","journal-title":"Nature"},{"key":"bib7","doi-asserted-by":"crossref","first-page":"3230","DOI":"10.1182\/blood.V88.8.3230.bloodjournal8883230","article-title":"An experimental model of idiopathic pneumonia syndrome after bone marrow transplantation: I. 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