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Tyner JW , Tognon CE , Bottomly D , Wilmot B , Kurtz SE , Savage SL , Long N , Schultz AR , Traer E , Abel M , Agarwal A , Blucher A , Borate U , Bryant J , Burke R , Carlos A , Carpenter R , Carroll J , Chang BH , Coblentz C , d'Almeida A , Cook R , Danilov A , Dao KT , Degnin M , Devine D , Dibb J , Edwards DKth , Eide CA , English I , Glover J , Henson R , Ho H , Jemal A , Johnson K , Johnson R , Junio B , Kaempf A , Leonard J , Lin C , Liu SQ , Lo P , Loriaux MM , Luty S , Macey T , MacManiman J , Martinez J , Mori M , Nelson D , Nichols C , Peters J , Ramsdill J , Rofelty A , Schuff R , Searles R , Segerdell E , Smith RL , Spurgeon SE , Sweeney T , Thapa A , Visser C , Wagner J , Watanabe-Smith K , Werth K , Wolf J , White L , Yates A , Zhang H , Cogle CR , Collins RH , Connolly DC , Deininger MW , Drusbosky L , Hourigan CS , Jordan CT , Kropf P , Lin TL , Martinez ME , Medeiros BC , Pallapati RR , Pollyea DA , Swords RT , Watts JM , Weir SJ , Wiest DL , Winters RM , McWeeney SK , Druker BJ
Functional genomic landscape of acute myeloid leukaemia
Nature. 2018 Oct;562(7728) :526-531
PMID: 30333627    PMCID: PMC6280667    URL: https://www.ncbi.nlm.nih.gov/pubmed/30333627
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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.
Notes
1476-4687 Tyner, Jeffrey W Tognon, Cristina E Bottomly, Daniel Wilmot, Beth Kurtz, Stephen E Savage, Samantha L Long, Nicola Schultz, Anna Reister Traer, Elie Abel, Melissa Agarwal, Anupriya Blucher, Aurora Borate, Uma Bryant, Jade Burke, Russell Carlos, Amy Carpenter, Richie Carroll, Joseph Chang, Bill H Coblentz, Cody d'Almeida, Amanda Cook, Rachel Danilov, Alexey Dao, Kim-Hien T Degnin, Michie Devine, Deirdre Dibb, James Edwards, David K 5th Eide, Christopher A English, Isabel Glover, Jason Henson, Rachel Ho, Hibery Jemal, Abdusebur Johnson, Kara Johnson, Ryan Junio, Brian Kaempf, Andy Leonard, Jessica Lin, Chenwei Liu, Selina Qiuying Lo, Pierrette Loriaux, Marc M 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 L Spurgeon, Stephen E Sweeney, Tyler Thapa, Aashis Visser, Corinne Wagner, Jake Watanabe-Smith, Kevin Werth, Kristen Wolf, Joelle White, Libbey Yates, Amy Zhang, Haijiao Cogle, Christopher R Collins, Robert H Connolly, Denise C Deininger, Michael W Drusbosky, Leylah Hourigan, Christopher S Jordan, Craig T Kropf, Patricia Lin, Tara L Martinez, Micaela E Medeiros, Bruno C Pallapati, Rachel R Pollyea, Daniel A Swords, Ronan T Watts, Justin M Weir, Scott J Wiest, David L Winters, Ryan M McWeeney, Shannon K Druker, Brian J Journal Article UL1 TR002369/TR/NCATS NIH HHS/ U54 CA224019/CA/NCI NIH HHS/ R01 CA214428/CA/NCI NIH HHS/ KL2 TR000152/TR/NCATS NIH HHS/ R01 CA183974/CA/NCI NIH HHS/ HHMI/Howard Hughes Medical Institute/ R01 AI110985/AI/NIAID NIH HHS/ T15 LM007088/LM/NLM NIH HHS/ U01 CA217862/CA/NCI NIH HHS/ P30 CA069533/CA/NCI NIH HHS/ Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramura England Nature. 2018 Oct;562(7728):526-531. doi: 10.1038/s41586-018-0623-z. Epub 2018 Oct 17.