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Integrative analysis of drug response and clinical outcome in acute myeloid leukemia.
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.
Afiliación
  • Bottomly D; Division of Bioinformatics and Computational Biology, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR 97239, USA; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA.
  • Long N; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA; Division of Hematology & Medical Oncology, Department of Medicine, Oregon Health & Science University, Portland, OR 97239, USA.
  • Schultz AR; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA; Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, OR 97239, USA.
  • Kurtz SE; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA; Division of Hematology & Medical Oncology, Department of Medicine, Oregon Health & Science University, Portland, OR 97239, USA.
  • Tognon CE; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA; Division of Hematology & Medical Oncology, Department of Medicine, Oregon Health & Science University, Portland, OR 97239, USA.
  • Johnson K; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA; Division of Hematology & Medical Oncology, Department of Medicine, Oregon Health & Science University, Portland, OR 97239, USA.
  • Abel M; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA; Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, OR 97239, USA.
  • Agarwal A; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA; Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, OR 97239, USA; Department of Molecular & Medical Genetics, Oregon Health & Science University, P
  • Avaylon S; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA; Division of Hematology & Medical Oncology, Department of Medicine, Oregon Health & Science University, Portland, OR 97239, USA.
  • Benton E; Division of Bioinformatics and Computational Biology, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR 97239, USA; Oregon Clinical and Translational Research Institute, Oregon Health & Science University, Portland, OR 97239, USA.
  • Blucher A; Division of Bioinformatics and Computational Biology, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR 97239, USA; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA.
  • Borate U; Division of Hematology, Department of Internal Medicine, James Cancer Center, Ohio State University, Columbus, OH 43210, USA.
  • Braun TP; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA; Division of Hematology & Medical Oncology, Department of Medicine, Oregon Health & Science University, Portland, OR 97239, USA.
  • Brown J; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA; Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, OR 97239, USA.
  • Bryant J; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA; Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, OR 97239, USA.
  • Burke R; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA; Division of Hematology & Medical Oncology, Department of Medicine, Oregon Health & Science University, Portland, OR 97239, USA.
  • Carlos A; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA; Integrated Genomics Laboratory, Oregon Health & Science University, Portland, OR 97239, USA.
  • Chang BH; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA; Division of Hematology and Oncology, Department of Pediatrics, Oregon Health & Science University, Portland, OR 97239, USA.
  • Cho HJ; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA; Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR 97239, USA.
  • Christy S; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA; Division of Hematology & Medical Oncology, Department of Medicine, Oregon Health & Science University, Portland, OR 97239, USA.
  • Coblentz C; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA; Division of Hematology & Medical Oncology, Department of Medicine, Oregon Health & Science University, Portland, OR 97239, USA.
  • Cohen AM; Division of Bioinformatics and Computational Biology, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR 97239, USA; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA; Oregon Clinical and Translatio
  • d'Almeida A; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA; Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, OR 97239, USA.
  • Cook R; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA; Division of Hematology & Medical Oncology, Department of Medicine, Oregon Health & Science University, Portland, OR 97239, USA.
  • Danilov A; Department of Hematology and Hematopoietic Stem Cell Transplant, City of Hope National Medical Center, Duarte, CA 91010, USA.
  • Dao KT; Astex Pharmaceuticals, Cambridge, CB4 0QA, UK.
  • Degnin M; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA; Division of Hematology & Medical Oncology, Department of Medicine, Oregon Health & Science University, Portland, OR 97239, USA.
  • Dibb J; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA; Division of Hematology & Medical Oncology, Department of Medicine, Oregon Health & Science University, Portland, OR 97239, USA.
  • Eide CA; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA; Division of Hematology & Medical Oncology, Department of Medicine, Oregon Health & Science University, Portland, OR 97239, USA.
  • English I; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA; Division of Hematology & Medical Oncology, Department of Medicine, Oregon Health & Science University, Portland, OR 97239, USA.
  • Hagler S; Division of Bioinformatics and Computational Biology, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR 97239, USA; Oregon Clinical and Translational Research Institute, Oregon Health & Science University, Portland, OR 97239, USA.
  • Harrelson H; Division of Bioinformatics and Computational Biology, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR 97239, USA; Oregon Clinical and Translational Research Institute, Oregon Health & Science University, Portland, OR 97239, USA.
  • Henson R; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA; Integrated Genomics Laboratory, Oregon Health & Science University, Portland, OR 97239, USA.
  • Ho H; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA; Division of Hematology & Medical Oncology, Department of Medicine, Oregon Health & Science University, Portland, OR 97239, USA.
  • Joshi SK; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA; Division of Hematology & Medical Oncology, Department of Medicine, Oregon Health & Science University, Portland, OR 97239, USA.
  • Junio B; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA; Division of Hematology & Medical Oncology, Department of Medicine, Oregon Health & Science University, Portland, OR 97239, USA.
  • Kaempf A; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA; Biostatistics Shared Resource, Oregon Health & Science University, Portland, OR 97239, USA.
  • Kosaka Y; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA; Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR 97239, USA.
  • Laderas T; DNA Nexus, Mountain View, CA 94040, USA.
  • Lawhead M; Division of Bioinformatics and Computational Biology, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR 97239, USA; Oregon Clinical and Translational Research Institute, Oregon Health & Science University, Portland, OR 97239, USA.
  • Lee H; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA; Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, OR 97239, USA.
  • Leonard JT; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA; Division of Hematology & Medical Oncology, Department of Medicine, Oregon Health & Science University, Portland, OR 97239, USA.
  • Lin C; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA; Integrated Genomics Laboratory, Oregon Health & Science University, Portland, OR 97239, USA.
  • Lind EF; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA; Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR 97239, USA.
  • Liu SQ; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA; Division of Hematology & Medical Oncology, Department of Medicine, Oregon Health & Science University, Portland, OR 97239, USA.
  • Lo P; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA; Division of Hematology & Medical Oncology, Department of Medicine, Oregon Health & Science University, Portland, OR 97239, USA.
  • Loriaux MM; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA; Department of Pathology, Oregon Health & Science University, Portland, OR 97239, USA.
  • Luty S; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA; Division of Hematology & Medical Oncology, Department of Medicine, Oregon Health & Science University, Portland, OR 97239, USA.
  • Maxson JE; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA; Division of Oncologic Sciences, Department of Medicine, Oregon Health & Science University, Portland, OR 97239, USA.
  • Macey T; Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA; Division of Hematology & Medical Oncology, Department of Medicine, Oregon Health & Science University, Portland, OR 97239, USA.
Cancer Cell ; 40(8): 850-864.e9, 2022 08 08.
Article en En | MEDLINE | ID: mdl-35868306
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Mieloide Aguda Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Cancer Cell Asunto de la revista: NEOPLASIAS Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Mieloide Aguda Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Cancer Cell Asunto de la revista: NEOPLASIAS Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos