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 Coblentz, Amanda 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 () and Brian J. Druker ()
Additional contact information
Jeffrey W. Tyner: Oregon Health & Science University
Cristina E. Tognon: Knight Cancer Institute, Oregon Health & Science University
Daniel Bottomly: Knight Cancer Institute, Oregon Health & Science University
Beth Wilmot: Knight Cancer Institute, Oregon Health & Science University
Stephen E. Kurtz: Knight Cancer Institute, Oregon Health & Science University
Samantha L. Savage: Oregon Health & Science University
Nicola Long: Knight Cancer Institute, Oregon Health & Science University
Anna Reister Schultz: Oregon Health & Science University
Elie Traer: Knight Cancer Institute, Oregon Health & Science University
Melissa Abel: Oregon Health & Science University
Anupriya Agarwal: Knight Cancer Institute, Oregon Health & Science University
Aurora Blucher: Knight Cancer Institute, Oregon Health & Science University
Uma Borate: Knight Cancer Institute, Oregon Health & Science University
Jade Bryant: Oregon Health & Science University
Russell Burke: Knight Cancer Institute, Oregon Health & Science University
Amy Carlos: Knight Cancer Institute, Oregon Health & Science University
Richie Carpenter: Knight Cancer Institute, Oregon Health & Science University
Joseph Carroll: Knight Cancer Institute, Oregon Health & Science University
Bill H. Chang: Knight Cancer Institute, Oregon Health & Science University
Cody Coblentz: Knight Cancer Institute, Oregon Health & Science University
Amanda d’Almeida: Oregon Health & Science University
Rachel Cook: Knight Cancer Institute, Oregon Health & Science University
Alexey Danilov: Knight Cancer Institute, Oregon Health & Science University
Kim-Hien T. Dao: Knight Cancer Institute, Oregon Health & Science University
Michie Degnin: Knight Cancer Institute, Oregon Health & Science University
Deirdre Devine: Knight Cancer Institute, Oregon Health & Science University
James Dibb: Knight Cancer Institute, Oregon Health & Science University
David K. Edwards: Oregon Health & Science University
Christopher A. Eide: Knight Cancer Institute, Oregon Health & Science University
Isabel English: Knight Cancer Institute, Oregon Health & Science University
Jason Glover: Knight Cancer Institute, Oregon Health & Science University
Rachel Henson: Knight Cancer Institute, Oregon Health & Science University
Hibery Ho: Knight Cancer Institute, Oregon Health & Science University
Abdusebur Jemal: Knight Cancer Institute, Oregon Health & Science University
Kara Johnson: Knight Cancer Institute, Oregon Health & Science University
Ryan Johnson: Knight Cancer Institute, Oregon Health & Science University
Brian Junio: Knight Cancer Institute, Oregon Health & Science University
Andy Kaempf: Knight Cancer Institute, Oregon Health & Science University
Jessica Leonard: Knight Cancer Institute, Oregon Health & Science University
Chenwei Lin: Knight Cancer Institute, Oregon Health & Science University
Selina Qiuying Liu: Knight Cancer Institute, Oregon Health & Science University
Pierrette Lo: Knight Cancer Institute, Oregon Health & Science University
Marc M. Loriaux: Knight Cancer Institute, Oregon Health & Science University
Samuel Luty: Knight Cancer Institute, Oregon Health & Science University
Tara Macey: Knight Cancer Institute, Oregon Health & Science University
Jason MacManiman: Oregon Health & Science University
Jacqueline Martinez: Oregon Health & Science University
Motomi Mori: Knight Cancer Institute, Oregon Health & Science University
Dylan Nelson: Oregon State University
Ceilidh Nichols: Knight Cancer Institute, Oregon Health & Science University
Jill Peters: Knight Cancer Institute, Oregon Health & Science University
Justin Ramsdill: Oregon Health & Science University
Angela Rofelty: Oregon Health & Science University
Robert Schuff: Oregon Health & Science University
Robert Searles: Knight Cancer Institute, Oregon Health & Science University
Erik Segerdell: Knight Cancer Institute, Oregon Health & Science University
Rebecca L. Smith: Knight Cancer Institute, Oregon Health & Science University
Stephen E. Spurgeon: Knight Cancer Institute, Oregon Health & Science University
Tyler Sweeney: Knight Cancer Institute, Oregon Health & Science University
Aashis Thapa: Knight Cancer Institute, Oregon Health & Science University
Corinne Visser: Knight Cancer Institute, Oregon Health & Science University
Jake Wagner: Knight Cancer Institute, Oregon Health & Science University
Kevin Watanabe-Smith: Knight Cancer Institute, Oregon Health & Science University
Kristen Werth: Knight Cancer Institute, Oregon Health & Science University
Joelle Wolf: Knight Cancer Institute, Oregon Health & Science University
Libbey White: Knight Cancer Institute, Oregon Health & Science University
Amy Yates: Oregon Health & Science University
Haijiao Zhang: Oregon Health & Science University
Christopher R. Cogle: University of Florida
Robert H. Collins: University of Texas Southwestern Medical Center
Denise C. Connolly: Molecular Therapeutics Program, Fox Chase Cancer Center
Michael W. Deininger: University of Utah
Leylah Drusbosky: University of Florida
Christopher S. Hourigan: National Heart, Lung and Blood Institute, National Institutes of Health
Craig T. Jordan: University of Colorado
Patricia Kropf: Bone Marrow Transplant Program, Fox Chase Cancer Center
Tara L. Lin: University of Kansas
Micaela E. Martinez: Clinical Research Services, University of Miami Sylvester Comprehensive Cancer Center
Bruno C. Medeiros: Stanford University
Rachel R. Pallapati: Clinical Research Services, University of Miami Sylvester Comprehensive Cancer Center
Daniel A. Pollyea: University of Colorado
Ronan T. Swords: University of Miami Sylvester Comprehensive Cancer Center
Justin M. Watts: University of Miami Sylvester Comprehensive Cancer Center
Scott J. Weir: University of Kansas Medical Center
David L. Wiest: Blood Cell Development and Function Program, Fox Chase Cancer Center
Ryan M. Winters: Fox Chase Cancer Center Biosample Repository Facility
Shannon K. McWeeney: Knight Cancer Institute, Oregon Health & Science University
Brian J. Druker: Knight Cancer Institute, Oregon Health & Science University

Nature, 2018, vol. 562, issue 7728, 526-531

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.

Keywords: Whole Exome Sequencing; Fms-related Tyrosine Kinase (FLT3); BCL6 Corepressor (BCOR); Ibrutinib; Weighted Gene Correlation Network Analysis (WGCNA) (search for similar items in EconPapers)
Date: 2018
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Citations: View citations in EconPapers (27)

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DOI: 10.1038/s41586-018-0623-z

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