| Literature DB >> 35868306 |
Daniel Bottomly1, Nicola Long2, Anna Reister Schultz3, Stephen E Kurtz2, Cristina E Tognon2, Kara Johnson2, Melissa Abel3, Anupriya Agarwal4, Sammantha Avaylon2, Erik Benton5, Aurora Blucher1, Uma Borate6, Theodore P Braun2, Jordana Brown3, Jade Bryant3, Russell Burke2, Amy Carlos7, Bill H Chang8, Hyun Jun Cho9, Stephen Christy2, Cody Coblentz2, Aaron M Cohen10, Amanda d'Almeida3, Rachel Cook2, Alexey Danilov11, Kim-Hien T Dao12, Michie Degnin2, James Dibb2, Christopher A Eide2, Isabel English2, Stuart Hagler5, Heath Harrelson5, Rachel Henson7, Hibery Ho2, Sunil K Joshi2, Brian Junio2, Andy Kaempf13, Yoko Kosaka9, Ted Laderas14, Matt Lawhead5, Hyunjung Lee3, Jessica T Leonard2, Chenwei Lin7, Evan F Lind9, Selina Qiuying Liu2, Pierrette Lo2, Marc M Loriaux15, Samuel Luty2, Julia E Maxson16, Tara Macey2, Jacqueline Martinez2, Jessica Minnier17, Andrea Monteblanco2, Motomi Mori18, Quinlan Morrow3, Dylan Nelson19, Justin Ramsdill5, Angela Rofelty3, Alexandra Rogers2, Kyle A Romine3, Peter Ryabinin1, Jennifer N Saultz2, David A Sampson2, Samantha L Savage2, Robert Schuff20, Robert Searles7, Rebecca L Smith2, Stephen E Spurgeon2, Tyler Sweeney2, Ronan T Swords2, Aashis Thapa2, Karina Thiel-Klare2, Elie Traer2, Jake Wagner2, Beth Wilmot5, Joelle Wolf2, Guanming Wu10, Amy Yates5, Haijiao Zhang16, Christopher R Cogle21, Robert H Collins22, Michael W Deininger23, Christopher S Hourigan24, Craig T Jordan25, Tara L Lin26, Micaela E Martinez27, Rachel R Pallapati27, Daniel A Pollyea25, Anthony D Pomicter28, Justin M Watts29, Scott J Weir30, Brian J Druker31, Shannon K McWeeney32, Jeffrey W Tyner33.
Abstract
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.Entities:
Keywords: JEDI; LSC17; MEGF12; cell state; eigengene; hematologic malignancy; leukemia stem cell; monocyte; targeted therapy
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Year: 2022 PMID： 35868306 PMCID： PMC9378589 DOI： 10.1016/j.ccell.2022.07.002
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 38.585