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Integrated stem cell signature and cytomolecular risk determination in pediatric acute myeloid leukemia

Author

Listed:
  • Benjamin J. Huang

    (University of California San Francisco
    University of California San Francisco)

  • Jenny L. Smith

    (Fred Hutchinson Cancer Research Center)

  • Jason E. Farrar

    (University of Arkansas for Medical Sciences & Arkansas Children’s Research Institute)

  • Yi-Cheng Wang

    (Children’s Oncology Group)

  • Masayuki Umeda

    (St. Jude Children’s Research Hospital)

  • Rhonda E. Ries

    (Fred Hutchinson Cancer Research Center)

  • Amanda R. Leonti

    (Fred Hutchinson Cancer Research Center)

  • Erin Crowgey

    (Nemours Center for Cancer and Blood Disorders and Alfred I. DuPont Hospital for Children)

  • Scott N. Furlan

    (Fred Hutchinson Cancer Research Center
    Seattle Children’s Hospital, University of Washington)

  • Katherine Tarlock

    (Fred Hutchinson Cancer Research Center
    Seattle Children’s Hospital, University of Washington)

  • Marcos Armendariz

    (University of California, San Francisco)

  • Yanling Liu

    (St. Jude Children’s Research Hospital)

  • Timothy I. Shaw

    (St. Jude Children’s Research Hospital)

  • Lisa Wei

    (Michael Smith Genome Sciences Centre)

  • Robert B. Gerbing

    (Children’s Oncology Group)

  • Todd M. Cooper

    (Seattle Children’s Hospital, University of Washington)

  • Alan S. Gamis

    (Children’s Mercy Hospitals and Clinics)

  • Richard Aplenc

    (Children’s Hospital of Philadelphia)

  • E. Anders Kolb

    (Nemours Center for Cancer and Blood Disorders and Alfred I. DuPont Hospital for Children)

  • Jeffrey Rubnitz

    (St. Jude Children’s Research Hospital)

  • Jing Ma

    (St. Jude Children’s Research Hospital)

  • Jeffery M. Klco

    (St. Jude Children’s Research Hospital)

  • Xiaotu Ma

    (St. Jude Children’s Research Hospital)

  • Todd A. Alonzo

    (University of Southern California)

  • Timothy Triche

    (Van Andel Research Institute)

  • Soheil Meshinchi

    (Fred Hutchinson Cancer Research Center
    Seattle Children’s Hospital, University of Washington)

Abstract

Relapsed or refractory pediatric acute myeloid leukemia (AML) is associated with poor outcomes and relapse risk prediction approaches have not changed significantly in decades. To build a robust transcriptional risk prediction model for pediatric AML, we perform RNA-sequencing on 1503 primary diagnostic samples. While a 17 gene leukemia stem cell signature (LSC17) is predictive in our aggregated pediatric study population, LSC17 is no longer predictive within established cytogenetic and molecular (cytomolecular) risk groups. Therefore, we identify distinct LSC signatures on the basis of AML cytomolecular subtypes (LSC47) that were more predictive than LSC17. Based on these findings, we build a robust relapse prediction model within a training cohort and then validate it within independent cohorts. Here, we show that LSC47 increases the predictive power of conventional risk stratification and that applying biomarkers in a manner that is informed by cytomolecular profiling outperforms a uniform biomarker approach.

Suggested Citation

  • Benjamin J. Huang & Jenny L. Smith & Jason E. Farrar & Yi-Cheng Wang & Masayuki Umeda & Rhonda E. Ries & Amanda R. Leonti & Erin Crowgey & Scott N. Furlan & Katherine Tarlock & Marcos Armendariz & Yan, 2022. "Integrated stem cell signature and cytomolecular risk determination in pediatric acute myeloid leukemia," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33244-6
    DOI: 10.1038/s41467-022-33244-6
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    References listed on IDEAS

    as
    1. Friedman, Jerome H. & Hastie, Trevor & Tibshirani, Rob, 2010. "Regularization Paths for Generalized Linear Models via Coordinate Descent," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 33(i01).
    2. Catherine C. Smith & Qi Wang & Chen-Shan Chin & Sara Salerno & Lauren E. Damon & Mark J. Levis & Alexander E. Perl & Kevin J. Travers & Susana Wang & Jeremy P. Hunt & Patrick P. Zarrinkar & Eric E. Sc, 2012. "Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia," Nature, Nature, vol. 485(7397), pages 260-263, May.
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