Functional genomic landscape of acute myeloid leukaemia

Jeffrey W. Tyner, Cristina E. Tognon, Daniel Bottomly, Beth Wilmot, Stephen E. Kurtz, Samantha L. Savage, Nicola Long, Anna Reister Schultz, Elie Traer, Melissa Abel, Anupriya Agarwal, Aurora Blucher, Uma Borate, Jade Bryant, Russell Burke, Amy Carlos, Richie Carpenter, Joseph Carroll, Bill H. Chang, Cody CoblentzAmanda d’Almeida, Rachel Cook, Alexey Danilov, Kim Hien T. Dao, Michie Degnin, Deirdre Devine, James Dibb, David K. Edwards, Christopher A. Eide, Isabel English, Jason Glover, Rachel Henson, Hibery Ho, Abdusebur Jemal, Kara Johnson, Ryan Johnson, Brian Junio, Andy Kaempf, Jessica Leonard, Chenwei Lin, Selina Qiuying Liu, Pierrette Lo, Marc M. Loriaux, Samuel Luty, Tara Macey, Jason MacManiman, Jacqueline Martinez, Motomi Mori, Dylan Nelson, Ceilidh Nichols, Jill Peters, Justin Ramsdill, Angela Rofelty, Robert Schuff, Robert Searles, Erik Segerdell, Rebecca L. Smith, Stephen E. Spurgeon, Tyler Sweeney, Aashis Thapa, Corinne Visser, Jake Wagner, Kevin Watanabe-Smith, Kristen Werth, Joelle Wolf, Libbey White, Amy Yates, Haijiao Zhang, Christopher R. Cogle, Robert H. Collins, Denise C. Connolly, Michael W. Deininger, Leylah Drusbosky, Christopher S. Hourigan, Craig T. Jordan, Patricia Kropf, Tara L. Lin, Micaela E. Martinez, Bruno C. Medeiros, Rachel R. Pallapati, Daniel A. Pollyea, Ronan T. Swords, Justin M. Watts, Scott J. Weir, David L. Wiest, Ryan M. Winters, Shannon K. McWeeney, Brian J. Druker

Research output: Contribution to journalArticle

122 Scopus citations

Abstract

The implementation of targeted therapies for acute myeloid leukaemia (AML) has been challenging because of the complex mutational patterns within and across patients as well as a dearth of pharmacologic agents for most mutational events. Here we report initial findings from the Beat AML programme on a cohort of 672 tumour specimens collected from 562 patients. We assessed these specimens using whole-exome sequencing, RNA sequencing and analyses of ex vivo drug sensitivity. Our data reveal mutational events that have not previously been detected in AML. We show that the response to drugs is associated with mutational status, including instances of drug sensitivity that are specific to combinatorial mutational events. Integration with RNA sequencing also revealed gene expression signatures, which predict a role for specific gene networks in the drug response. Collectively, we have generated a dataset—accessible through the Beat AML data viewer (Vizome)—that can be leveraged to address clinical, genomic, transcriptomic and functional analyses of the biology of AML.

Original languageEnglish (US)
Pages (from-to)526-531
Number of pages6
JournalNature
Volume562
Issue number7728
DOIs
StatePublished - Oct 25 2018

ASJC Scopus subject areas

  • General

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    Tyner, J. W., Tognon, C. E., Bottomly, D., Wilmot, B., Kurtz, S. E., Savage, S. L., Long, N., Schultz, A. R., Traer, E., Abel, M., Agarwal, A., Blucher, A., Borate, U., Bryant, J., Burke, R., Carlos, A., Carpenter, R., Carroll, J., Chang, B. H., ... Druker, B. J. (2018). Functional genomic landscape of acute myeloid leukaemia. Nature, 562(7728), 526-531. https://doi.org/10.1038/s41586-018-0623-z