The stem cell-associated gene expression signature allows risk stratification in pediatric acute myeloid leukemia

ABSTRACT Despite constant progress in prognostic risk stratification, children with acute myeloid leukemia (AML) still relapse. Treatment failure and subsequent relapse have been attributed

to acute myeloid leukemia-initiating cells (LSC), which harbor stem cell properties and are inherently chemoresistant. Although pediatric and adult AML represent two genetically very

distinct diseases, we reasoned that common LSC gene expression programs are shared and consequently, the highly prognostic LSC17 signature score recently developed in adults may also be of

clinical interest in childhood AML. Here, we demonstrated prognostic relevance of the LSC17 score in pediatric non-core-binding factor AML using Nanostring technology (ELAM02) and RNA-seq

data from the NCI (TARGET-AML). AML were stratified by LSC17 quartile groups (lowest 25%, intermediate 50% and highest 25%) and children with low LSC17 score had significantly better

event-free survival (EFS: HR = 3.35 (95%CI = 1.64–6.82), _P_ < 0.001) and overall survival (OS: HR = 3.51 (95%CI = 1.38–8.92), _P_ = 0.008) compared with patients with high LSC17 scores.

More importantly, the high LSC17 score was an independent negative EFS and OS prognosticator determined by multivariate Cox model analysis (EFS: HR = 3.42 (95% CI = 1.63–7.16), _P_ = 0.001;

OS HR = 3.02 (95%CI = 1.16–7.85), _P_ = 0.026). In conclusion, we have demonstrated the broad applicability of the LSC17 score in the clinical management of AML by extending its prognostic

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our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS INTEGRATED STEM CELL SIGNATURE AND CYTOMOLECULAR RISK DETERMINATION IN PEDIATRIC ACUTE MYELOID LEUKEMIA Article

Open access 19 September 2022 SINGLE-CELL ANALYSIS REVEALS ALTERED TUMOR MICROENVIRONMENTS OF RELAPSE- AND REMISSION-ASSOCIATED PEDIATRIC ACUTE MYELOID LEUKEMIA Article Open access 05

October 2023 MULTIOMIC SINGLE CELL SEQUENCING IDENTIFIES STEMLIKE NATURE OF MIXED PHENOTYPE ACUTE LEUKEMIA Article Open access 18 September 2024 REFERENCES * Ward E, DeSantis C, Robbins A,

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Working Party. Blood. 2018;131:1275–91. Article  CAS  Google Scholar  Download references ACKNOWLEDGEMENTS We thank all the patients, their families, and the staff of all the centers of

Société Française des Cancers de l’Enfant (SFCE) for their implication in the trial. The results published here are in part based upon data generated by the TARGET initiative managed by the

NCI. The AML Project data used for this analysis are available at https://ocg.cancer.gov/programs/target/data-matrix. More Information about TARGET can be found at

http://ocg.cancer.gov/programs/target. FUNDING This work was supported by the French National Cancer Institute (INCA-DGOS_5797) and by a grant from the French Ministry of Health (PHRC-K 2003

no 03142). The Trousseau laboratory received funding from the Association Laurette Fugain and La Fondation de France to support molecular study and the ELAM02 national tumor Bank.

Integrated research program: pediatric cancer PAIR grant: CONECT-AML INCA PRT-K: CAMELIA. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Laboratory of Hematology, CHU Lille, Lille, France

Nicolas Duployez, Alice Marceau-Renaut & Claude Preudhomme * UMR-S 1172, JPArc - Jean-Pierre AUBERT Research Center Neurosciences et Cancer, Univ. Lille, Inserm, CHU Lille, Lille, France

Nicolas Duployez, Alice Marceau-Renaut, Fanny Gonzales, Adeline Barthélémy, Claude Preudhomme & Meyling Cheok * Functional Genomics Platform, Univ. Lille, Lille, France Céline Villenet,

 Frédéric Leprêtre, Guy Leverger & Martin Figeac * Department of Pediatric Hematology and Oncology, APHP, Trousseau Hospital, GH HUEP, Paris, France Arnaud Petit * Department of Clinical

Pharmacology and Clinical Research Unit of East of Paris, APHP, Saint Antoine Hospital, Paris, France Alexandra Rousseau * Institute of Biomaterials and Biomedical Engineering, University

of Toronto, Toronto, ON, Canada Stanley W. K. Ng * IPMC, Université Côte d’Azur, CNRS, Valbonne, France Agnès Paquet * Department of Pediatric Hematology-Oncology, CHU Lille, Lille, France

Fanny Gonzales & Brigitte Nelken * Department of Biochemistry, CHU Lille, Lille, France Nicolas Pottier * Department of Pediatric Hematology, CHU Marseille, La Timone, Marseille, France

Gérard Michel * Department of Pediatric Hematology and Immunology, APHP, Robert Debré University Hospital, Paris, France André Baruchel * Institute of Hematology and Oncology Pediatrics,

Hospices Civils, Claude Bernard University, Lyon, France Yves Bertrand * Laboratory of Hematology, APHP, Trousseau Hospital, GH HUEP, Paris, France Hélène Lapillonne * Department of

Molecular Genetics, University of Toronto, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada John E. Dick & Jean C. Y. Wang Authors * Nicolas Duployez View

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publications You can also search for this author inPubMed Google Scholar * Meyling Cheok View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS GL

was the principal investigator of the ELAM02 trial. AP, FG, BN, GM, AB, YB, GL enrolled patients in the study. AR ensured database management. ND, AMR, CP, and HL performed genetic

analysis. SN, JW, and JD provided materials and protocols. ND, CV, FL, MF, MC performed Nanostring assay and analyzed data. AP and MC performed statistical analysis. ND, AB, NP, CP, and MC

wrote the manuscript which was approved by all the authors. CORRESPONDING AUTHORS Correspondence to Nicolas Duployez or Meyling Cheok. ETHICS DECLARATIONS CONFLICT OF INTEREST The authors

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ARTICLE Duployez, N., Marceau-Renaut, A., Villenet, C. _et al._ The stem cell-associated gene expression signature allows risk stratification in pediatric acute myeloid leukemia. _Leukemia_

33, 348–357 (2019). https://doi.org/10.1038/s41375-018-0227-5 Download citation * Received: 05 April 2018 * Revised: 20 June 2018 * Accepted: 10 July 2018 * Published: 08 August 2018 * Issue

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