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Cited by 403Acute Myeloid Leukemia ResearchRetinoids in leukemia and cellular processesChronic Myeloid Leukemia Treatments

Integrative Analysis of Drug Response and Clinical Outcome in Acute Myeloid Leukemia

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Bottomly, Daniel, Long, Nicola, Schultz, Anna Reister, Kurtz, Stephen E., Tognon, Cristina E., Johnson, Kara, Abel, Melissa, Agarwal, Anupriya +86 more·2022·Cancer Cell
DOI 10.1016/j.ccell.2022.07.002PMC PMC9378589
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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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  • Among 671 individuals with AML, individuals with high FOXN1 activity level tend to have a higher survival probability (two-sided log-rank test).

    “we calculated the TF activity of the transcriptome profile (bulk RNA-seq data) of 671 individuals with AML73 and performed survival analysis, which indicated that individuals with high FOXN1 activity level tend to have a higher survival probability (Fig. 6c).”

    From Inferring gene regulatory networks from single-cell multiome data using atlas-scale external data (2025) · cites this paper as [73]

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Authors
Bottomly, D., Long, N., Schultz, A. R., Kurtz, S. E., Tognon, C. E., Johnson, K., Abel, M., Agarwal, A., Avaylon, S., Benton, E., Blucher, A., Borate, U., Braun, T. P., Brown, J., Bryant, J., Burke, R., Carlos, A., Chang, B. H., Cho, H. J., Christy, S., Coblentz, C., Cohen, A. M., d’Almeida, A., Cook, R., Danilov, A., Dao, K.-H. T., Degnin, M., Dibb, J., Eide, C. A., English, I., Hagler, S., Harrelson, H., Henson, R., Ho, H., Joshi, S. K., Junio, B., Kaempf, A., Kosaka, Y., Laderas, T., Lawhead, M., Lee, H., Leonard, J. T., Lin, C., Lind, E. F., Liu, S. Q., Lo, P., Loriaux, M. M., Luty, S., Maxson, J. E., Macey, T., Martinez, J., Minnier, J., Monteblanco, A., Mori, M., Morrow, Q., Nelson, D., Ramsdill, J., Rofelty, A., Rogers, A., Romine, K. A., Ryabinin, P., Saultz, J. N., Sampson, D. A., Savage, S. L., Schuff, R., Searles, R., Smith, R. L., Spurgeon, S. E., Sweeney, T., Swords, R. T., Thapa, A., Thiel-Klare, K., Traer, E., Wagner, J., Wilmot, B., Wolf, J., Wu, G., Yates, A., Zhang, H., Cogle, C. R., Collins, R. H., Deininger, M. W., Hourigan, C. S., Jordan, C. T., Lin, T. L., Martinez, M. E., Pallapati, R. R., Pollyea, D. A., Pomicter, A. D., Watts, J. M., Weir, S. J., Druker, B. J., McWeeney, S. K., & Tyner, J. W.
Affiliations
  • Oregon Health & Science University (US)
  • The Ohio State University (US)
  • City Of Hope National Medical Center (US)
  • DNAnexus (United States) (US)
  • St. Jude Children's Research Hospital (US)
  • Oregon State University (US)
  • Ochin (US)
  • University of Florida (US)
  • The University of Texas Southwestern Medical Center (US)
  • University of Utah (US)
  • National Institutes of Health (US)
  • University of Colorado Denver (US)
  • University of Kansas (US)
  • University of Miami (US)
  • The University of Kansas Cancer Center (US)
Corresponding author
  • Druker, Brian J.
  • McWeeney, Shannon K.
  • Tyner, Jeffrey W.
ORCID
Venue
Cancer Cell
Publisher
Elsevier BV
Published
2022-08
Volume
40
Issue
8
Pages
850-864.e9
ISSN
1535-6108 (ISSN-L)
DOI
10.1016/j.ccell.2022.07.002
PMC
PMC9378589
OpenAlex
W4286512367
Cited by
403
References
9
Citations by year
2026: 110 · 2025: 117 · 2024: 105 · 2023: 57 · 2022: 13 · 2020: 1
FWCI
54.62
Type
journal article
Language
en
Open access
Licence
Locations
  • Cancer Cell (publishedVersion, cc-by-nc-nd)
  • SSRN Electronic Journal (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (P30CA042014)
  • University of Utah (2400-13)
  • National Cancer Institute (RSG-19-184-01 \u2013 LIB, R00 5K99CA237630, R01CA229875, R01 CA247943, U01CA217862, R01CA214428, U01CA214116, U54CA224019, F30CA239335)
  • Silver Family Foundation
  • Oregon Health and Science University
  • Gabrielle's Angel Foundation for Cancer Research
  • National Heart, Lung, and Blood Institute (R01HL155426)
  • American Cancer Society (RSG-17-187-01-LIB)
  • Gilead Sciences
  • Iterion Therapeutics
  • Novartis
  • Mark Foundation For Cancer Research
  • Bristol-Myers Squibb
  • National Center for Advancing Translational Sciences (UL1TR002369)
  • American Society of Hematology (K08 CA245224)
  • Otago Medical Research Foundation
  • AstraZeneca
  • Leukemia and Lymphoma Society
  • Howard Hughes Medical Institute
  • V Foundation for Cancer Research (F30CA239335, RSG-19-184-01 \u2013 LIB)
  • AbbVie
  • Agios Pharmaceuticals
  • Servier
  • Pfizer
  • Incyte
Topics
  • Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
  • Health Sciences › Medicine › Hematology › Chronic Myeloid Leukemia Treatments
Keywords
acute myeloid leukemia, drug sensitivity, ex vivo drug response, PEAR1, survival prediction, clinical outcomes
MeSH terms
Cell Differentiation, Humans, Receptors, Cell Surface, Cohort Studies, Leukemia, Myeloid, Acute, Transcriptome

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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