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Cancer cell · 2022

Integrative analysis of drug response and clinical outcome in acute myeloid leukemia.

СтатьяПоддержка исследования: вне правительства СШАПоддержка NIH: внешняя программаНазвание и аннотация: Перевод пока не подготовлен
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Bottomly Daniel, Long Nicola, Schultz Anna Reister, Kurtz Stephen E, Tognon Cristina E, Johnson Kara, Abel Melissa, Agarwal Anupriya, Avaylon Sammantha, Benton Erik, Blucher Aurora, Borate Uma, Braun Theodore P, Brown Jordana, Bryant Jade, Burke Russell, Carlos Amy, Chang Bill H, Cho Hyun Jun, Christy Stephen, Coblentz Cody, Cohen Aaron M, d'Almeida Amanda, Cook Rachel, Danilov Alexey, Dao Kim-Hien T, Degnin Michie, Dibb James, Eide Christopher A, English Isabel, Hagler Stuart, Harrelson Heath, Henson Rachel, Ho Hibery, Joshi Sunil K, Junio Brian, Kaempf Andy, Kosaka Yoko, Laderas Ted, Lawhead Matt, Lee Hyunjung, Leonard Jessica T, Lin Chenwei, Lind Evan F, Liu Selina Qiuying, Lo Pierrette, Loriaux Marc M, Luty Samuel, Maxson Julia E, Macey Tara, Martinez Jacqueline, Minnier Jessica, Monteblanco Andrea, Mori Motomi, Morrow Quinlan, Nelson Dylan, Ramsdill Justin, Rofelty Angela, Rogers Alexandra, Romine Kyle A, Ryabinin Peter, Saultz Jennifer N, Sampson David A, Savage Samantha L, Schuff Robert, Searles Robert, Smith Rebecca L, Spurgeon Stephen E, Sweeney Tyler, Swords Ronan T, Thapa Aashis, Thiel-Klare Karina, Traer Elie, Wagner Jake, Wilmot Beth, Wolf Joelle, Wu Guanming, Yates Amy, Zhang Haijiao, Cogle Christopher R, Collins Robert H, Deininger Michael W, Hourigan Christopher S, Jordan Craig T, Lin Tara L, Martinez Micaela E, Pallapati Rachel R, Pollyea Daniel A, Pomicter Anthony D, Watts Justin M, Weir Scott J, Druker Brian J, McWeeney Shannon K, Tyner Jeffrey W

Аннотация

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.

Предметные рубрики MeSH

ИП Урсолов Владлен Сергеевич

ИНН 500118482352 · ОГРНИП 314500117700049

Реквизиты и контакты