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

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, Yanling Liu, Timothy I. Shaw, Lisa Wei, Robert B. Gerbing, Todd M. Cooper, Alan S. Gamis, Richard Aplenc, E. Anders Kolb, Jeffrey Rubnitz, Jing Ma, Jeffery M. Klco, Xiaotu Ma, Todd A. Alonzo, Timothy Triche and Soheil Meshinchi
Additional contact information
Benjamin J. Huang: 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
Katherine Tarlock: Fred Hutchinson Cancer Research Center
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

Nature Communications, 2022, vol. 13, issue 1, 1-11

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-33244-6

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