Functional genomic landscape of acute myeloid leukaemia. (25th October 2018)

• Record Type: Journal Article
• Authors: Tyner, Jeffrey; Tognon, Cristina; Bottomly, Daniel; Wilmot, Beth; Kurtz, Stephen; Savage, Samantha; Long, Nicola; Schultz, Anna; Traer, Elie; Abel, Melissa; Agarwal, Anupriya; Blucher, Aurora; Borate, Uma; Bryant, Jade; Burke, Russell; Carlos, Amy; Carpenter, Richie; Carroll, Joseph; Chang, Bill; Coblentz, Cody; d'Almeida, Amanda; Cook, Rachel; Danilov, Alexey; Dao, Kim-Hien; Degnin, Michie; Devine, Deirdre; Dibb, James; Edwards, David; Eide, Christopher; English, Isabel; Glover, Jason; Henson, Rachel; Ho, Hibery; Jemal, Abdusebur; Johnson, Kara; Johnson, Ryan; Junio, Brian; Kaempf, Andy; Leonard, Jessica; Lin, Chenwei; Liu, Selina; Lo, Pierrette; Loriaux, Marc; Luty, Samuel; Macey, Tara; MacManiman, Jason; Martinez, Jacqueline; Mori, Motomi; Nelson, Dylan; Nichols, Ceilidh; Peters, Jill; Ramsdill, Justin; Rofelty, Angela; Schuff, Robert; Searles, Robert; Segerdell, Erik; Smith, Rebecca; Spurgeon, Stephen; Sweeney, Tyler; Thapa, Aashis; Visser, Corinne; Wagner, Jake; Watanabe-Smith, Kevin; Werth, Kristen; Wolf, Joelle; White, Libbey; Yates, Amy; Zhang, Haijiao; Cogle, Christopher; Collins, Robert; Connolly, Denise; Deininger, Michael; Drusbosky, Leylah; Hourigan, Christopher; Jordan, Craig; Kropf, Patricia; Lin, Tara; Martinez, Micaela; Medeiros, Bruno; Pallapati, Rachel; Pollyea, Daniel; Swords, Ronan; Watts, Justin; Weir, Scott; Wiest, David; Winters, Ryan; McWeeney, Shannon; Druker, Brian;
• Is Part Of: Nature. Volume 562:Number 7728(2018)
• Page Start: 526
• Page End: 531
• Publication Date: 2018-10-25
• Subjects: Science -- Periodicals; 505
• DOI: 10.1038/s41586-018-0623-z
• Languages: English
• ISSNs: 0028-0836

Abstract

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. Analyses of samples from patients with acute myeloid leukaemia reveal that drug response is associated with mutational status and gene expression; the generated dataset provides a basis for future clinical and functional studies of this disease.