作者
Daniel Bottomly,Nicola Long,Anna Reister Schultz,Stephen E. Kurtz,Cristina E. Tognon,Kara Johnson,Melissa L. Abel,Anupriya Agarwal,Sammantha Avaylon,Erik Benton,Aurora Blucher,Uma Borate,Theodore P. Braun,Jordana Brown,Jade Bryant,Russell T. Burke,Amy S. Carlos,Bill H. Chang,Hyun Jun Cho,Stephen Christy,Cody Coblentz,Aaron M. Cohen,Amanda d’Almeida,Rachel J. Cook,Alexey V. Danilov,Kim-Hien Dao,Michie Degnin,James Dibb,Christopher A. Eide,Isabel English,Stuart Hagler,Heath Harrelson,Rachel Henson,Hibery Ho,Sunil Kumar Joshi,Brian Junio,Andy Kaempf,Yoko Kosaka,Ted Laderas,Matt Lawhead,Hyunjung Lee,Jessica T. Leonard,Chenwei Lin,Evan Lind,Selina Qiuying Liu,Pierrette Lo,Marc M. Loriaux,Samuel B. Luty,Julia E. Maxson,Tara A. Macey,Jacqueline Martinez,Jessica Minnier,Andrea Monteblanco,Motomi Mori,Quinlan Morrow,Dylan Nelson,Justin W Ramsdill,Angela Rofelty,Alexandra Rogers,Kyle A. Romine,Peter Ryabinin,Jennifer N. Saultz,David A. Sampson,Samantha Savage,Robert Schuff,Robert P. Searles,Rebecca L. Smith,Stephen E. Spurgeon,Tyler Sweeney,Ronan T. Swords,Aashis Thapa,Karina Thiel-Klare,Elie Traer,Jesse Wagner,Beth Wilmot,Joelle Wolf,Guanming Wu,Amy Yates,Haijiao Zhang,Christopher R. Cogle,Robert H. Collins,Michael W. Deininger,Christopher S. Hourigan,Craig T. Jordan,Tara L. Lin,Micaela Martinez,Rachel R. Pallapati,Daniel A. Pollyea,Anthony D. Pomicter,Justin M. Watts,Scott J. Weir,Brian J. Druker,Shannon K. McWeeney,Jeffrey W. Tyner
摘要
Acute myeloid leukemia (AML) is a cancer of myeloid-lineage cells with limited therapeutic options. We previously combined ex vivo drug sensitivity with genomic, transcriptomic, and clinical annotations for a large cohort of AML patients, which facilitated discovery of functional genomic correlates. Here, we present a dataset that has been harmonized with our initial report to yield a cumulative cohort of 805 patients (942 specimens). We show strong cross-cohort concordance and identify features of drug response. Further, deconvoluting transcriptomic data shows that drug sensitivity is governed broadly by AML cell differentiation state, sometimes conditionally affecting other correlates of response. Finally, modeling of clinical outcome reveals a single gene, PEAR1, to be among the strongest predictors of patient survival, especially for young patients. Collectively, this report expands a large functional genomic resource, offers avenues for mechanistic exploration and drug development, and reveals tools for predicting outcome in AML.