小柯机器人

美国俄勒冈健康与科学大学Jeffrey W. Tyner，Shannon K. McWeeney和Brian J. Druker共同合作近期取得重要工作进展，他们共同研究提出了急性骨髓系白血病的药物反应和临床结果的综合分析。相关研究结果2022年7月21日在线出版于《癌细胞》杂志上。

研究人员之前将离体药物敏感性与一大批AML患者的基因组、转录组和临床注释相结合，这有助于发现功能基因组相关性。在这里，他们提供了一个数据集，该数据集与他们的初始报告相一致，得到了805名患者（942个样本）的累积队列。研究人员展示了强大的跨队列一致性并确定了药物反应的特征。此外，反卷积转录组数据表明，药物敏感性在很大程度上受AML细胞分化状态的控制，有时有条件地影响其他相关反应。最后，临床结果模型显示，单个基因PEAR1是患者生存的最强预测因子之一，尤其是对于年轻患者。

总的来说，本报告扩展了一个大型功能性基因组资源，为机制探索和药物开发提供了途径，并揭示了AML预后的预测工具。

据介绍，急性髓系白血病（AML）是一种治疗选择有限的髓系细胞癌症。

附：英文原文

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

Author: Daniel Bottomly, Nicola Long, Anna Reister Schultz, Stephen E. Kurtz, Cristina E. Tognon, Kara Johnson, Melissa Abel, Anupriya Agarwal, Sammantha Avaylon, Erik Benton, Aurora Blucher, Uma Borate, Theodore P. Braun, Jordana Brown, Jade Bryant, Russell Burke, Amy Carlos, Bill H. Chang, Hyun Jun Cho, Stephen Christy, Cody Coblentz, Aaron M. Cohen, Amanda d’Almeida, Rachel Cook, Alexey Danilov, Kim-Hien T. Dao, Michie Degnin, James Dibb, Christopher A. Eide, Isabel English, Stuart Hagler, Heath Harrelson, Rachel Henson, Hibery Ho, Sunil K. Joshi, Brian Junio, Andy Kaempf, Yoko Kosaka, Ted Laderas, Matt Lawhead, Hyunjung Lee, Jessica T. Leonard, Chenwei Lin, Evan F. Lind, Selina Qiuying Liu, Pierrette Lo, Marc M. Loriaux, Samuel Luty, Julia E. Maxson, Tara Macey, Jacqueline Martinez

Issue&Volume: 2022-07-21

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.

DOI: 10.1016/j.ccell.2022.07.002

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(22)00312-9

Cancer Cell：《癌细胞》，创刊于2002年。隶属于细胞出版社，最新IF：38.585
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